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1. PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines

Author

Feola, Sara, Chiaro, Jacopo, Fusciello, Manlio, Russo, Salvatore, Kleino, Iivari, Ylösmäki, Leena, Kekäläinen, Eliisa, Hästbacka, Johanna, Pekkarinen, Pirkka T., Ylösmäki, Erkko, Capone, Stefania, Folgori, Antonella, Raggioli, Angelo, Boni, Carolina, Tiezzi, Camilla, Vecchi, Andrea, Gelzo, Monica, Kared, Hassen, Nardin, Alessandra, Fehlings, Michael, Barban, Veronique, Ahokas, Petra, Viitala, Tapani, Castaldo, Giuseppe, Pastore, Lucio, Porter, Paul, Pesonen, Sari, and Cerullo, Vincenzo

Published
2024
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6. List of contributors

Author

Adamik, Juraj, primary, Aurisicchio, Luigi, additional, Bell, John C., additional, Bourgeois-Daigneault, Marie-Claude, additional, Butterfield, Lisa H., additional, Cerullo, Vincenzo, additional, Chiang, Cheryl L.-L., additional, Ciliberto, Gennaro, additional, Conforti, Antonella, additional, Finn, Olivera J., additional, Galli, Maria Cristina, additional, Hadrup, Sine Reker, additional, Hamilton, Duane H., additional, Hawthorne, Jenci, additional, Himuro, Hidetomo, additional, Jacqueline, Camille, additional, Jochems, Caroline, additional, Kadivar, Mohammad, additional, Kandalaft, Lana E., additional, Melief, Cornelis J.M., additional, Munson, Paul V., additional, Nappi, Filomena, additional, Palombo, Fabio, additional, Rammensee, Hans-Georg, additional, Sasada, Tetsuro, additional, Schlom, Jeffrey, additional, Shirwan, Haval, additional, Tagliamonte, Maria, additional, van der Gracht, Esmé T.I., additional, Wiekmeijer, Anna-Sophia, additional, Ylösmäki, Erkko, additional, and Yolcu, Esma, additional

Published
2022
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7. Artificially cloaked viral nanovaccine for cancer immunotherapy

Author

Fusciello, Manlio, Fontana, Flavia, Tähtinen, Siri, Capasso, Cristian, Feola, Sara, Martins, Beatriz, Chiaro, Jacopo, Peltonen, Karita, Ylösmäki, Leena, Ylösmäki, Erkko, Hamdan, Firas, Kari, Otto K., Ndika, Joseph, Alenius, Harri, Urtti, Arto, Hirvonen, Jouni T., Santos, Hélder A., and Cerullo, Vincenzo

Published
2019
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8. Data from Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna H.E., primary, Whalley, Thomas, primary, Capasso, Cristian, primary, Grönholm, Mikaela, primary, Feola, Sara, primary, Peltonen, Karita, primary, Hamdan, Firas, primary, Hernberg, Micaela, primary, Mäkelä, Siru, primary, Karhapää, Hanna, primary, Brown, Paul E., primary, Martins, Beatriz, primary, Fusciello, Manlio, primary, Ylösmäki, Erkko O., primary, Greco, Dario, primary, Kreutzman, Anna S., primary, Mustjoki, Satu, primary, Szomolay, Barbara, primary, and Cerullo, Vincenzo, primary

Published
2023
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9. Supplementary Tables and Figures from Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna H.E., primary, Whalley, Thomas, primary, Capasso, Cristian, primary, Grönholm, Mikaela, primary, Feola, Sara, primary, Peltonen, Karita, primary, Hamdan, Firas, primary, Hernberg, Micaela, primary, Mäkelä, Siru, primary, Karhapää, Hanna, primary, Brown, Paul E., primary, Martins, Beatriz, primary, Fusciello, Manlio, primary, Ylösmäki, Erkko O., primary, Greco, Dario, primary, Kreutzman, Anna S., primary, Mustjoki, Satu, primary, Szomolay, Barbara, primary, and Cerullo, Vincenzo, primary

Published
2023
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10. Supplementary Data File S1 from Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna H.E., primary, Whalley, Thomas, primary, Capasso, Cristian, primary, Grönholm, Mikaela, primary, Feola, Sara, primary, Peltonen, Karita, primary, Hamdan, Firas, primary, Hernberg, Micaela, primary, Mäkelä, Siru, primary, Karhapää, Hanna, primary, Brown, Paul E., primary, Martins, Beatriz, primary, Fusciello, Manlio, primary, Ylösmäki, Erkko O., primary, Greco, Dario, primary, Kreutzman, Anna S., primary, Mustjoki, Satu, primary, Szomolay, Barbara, primary, and Cerullo, Vincenzo, primary

Published
2023
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11. Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses

Author

CTI Leusen, Cancer, Infection & Immunity, Hamdan, Firas, Feodoroff, Michaela, Russo, Salvatore, Fusciello, Manlio, Feola, Sara, Chiaro, Jacopo, Antignani, Gabriella, Greco, Francesca, Leusen, Jeanette, Ylösmäki, Erkko, Grönholm, Mikaela, Cerullo, Vincenzo, CTI Leusen, Cancer, Infection & Immunity, Hamdan, Firas, Feodoroff, Michaela, Russo, Salvatore, Fusciello, Manlio, Feola, Sara, Chiaro, Jacopo, Antignani, Gabriella, Greco, Francesca, Leusen, Jeanette, Ylösmäki, Erkko, Grönholm, Mikaela, and Cerullo, Vincenzo

Published
2023

12. Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform

Author

Ylösmäki, Erkko, Ylösmäki, Leena, Fusciello, Manlio, Martins, Beatriz, Ahokas, Petra, Cojoc, Hanne, Uoti, Arttu, Feola, Sara, Kreutzman, Anna, Ranki, Tuuli, Karbach, Julia, Viitala, Tapani, Priha, Petri, Jäger, Elke, Pesonen, Sari, Cerullo, Vincenzo, Division of Pharmaceutical Biosciences, ImmunoViroTherapy Lab, Drug Research Program, TRIMM - Translational Immunology Research Program, HUSLAB, Divisions of Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, Pharmaceutical biophysics group, and Digital Precision Cancer Medicine (iCAN)

Subjects
317 Pharmacy, T cell activation, 3122 Cancers, oncolytic vaccine, CD40L, Original Article, PeptiCRAd, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, OX40L
Abstract

Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including various cytokines or chemokines. Here, we have developed a novel adenovirus encoding two immunostimulatory molecules: cluster of differentiation 40 ligand (CD40L) and tumor necrosis factor receptor superfamily member 4 ligand (OX40L). This novel virus, designated VALO-D102, is designed to activate both innate and adaptive immune responses against tumors. CD40L affects the innate side by licensing antigen-presenting cells to drive CD8+ T cell responses, and OX40L increases clonal expansion and survival of CD8+ T cells and formation of a larger pool of memory T cells. VALO-D102 and its murine surrogate VALO-mD901, expressing murine OX40L and CD40L, were used in our previously developed PeptiCRAd cancer vaccine platform. Intratumoral administration of PeptiCRAd significantly increased tumor-specific T cell responses, reduced tumor growth, and induced systemic anti-cancer immunity in two mouse models of melanoma. In addition, PeptiCRAd therapy, in combination with anti-PD-1 immune checkpoint inhibitor therapy, significantly improved tumor growth control as compared to either monotherapy alone., Graphical Abstract, Ylösmäki et al. develop an oncolytic adenovirus expressing immunostimulatory cytokines OX40L and CD40L. This virus was tested in a peptide-based cancer vaccine platform called PeptiCRAd. Intratumoral administration of PeptiCRAd induced systemic and intratumoral tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to immune checkpoint inhibitor therapy.

Published
2021

13. Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine

Author

Feola, Sara, primary, Russo, Salvatore, additional, Martins, Beatriz, additional, Lopes, Alessandra, additional, Vandermeulen, Gaëlle, additional, Fluhler, Vinciane, additional, De Giorgi, Camilla, additional, Fusciello, Manlio, additional, Pesonen, Sari, additional, Ylösmäki, Erkko, additional, Antignani, Gabriella, additional, Chiaro, Jacopo, additional, Hamdan, Firas, additional, Feodoroff, Michaela, additional, Grönholm, Mikaela, additional, and Cerullo, Vincenzo, additional

Published
2022
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14. A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Author

Feola, Sara, primary, Chiaro, Jacopo, additional, Martins, Beatriz, additional, Russo, Salvatore, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko, additional, Bonini, Chiara, additional, Ruggiero, Eliana, additional, Hamdan, Firas, additional, Feodoroff, Michaela, additional, Antignani, Gabriella, additional, Viitala, Tapani, additional, Pesonen, Sari, additional, Grönholm, Mikaela, additional, Branca, Rui MM, additional, Lehtiö, Janne, additional, and Cerullo, Vincenzo, additional

Published
2022
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16. Author response: A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Author

Feola, Sara, primary, Chiaro, Jacopo, additional, Martins, Beatriz, additional, Russo, Salvatore, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko, additional, Bonini, Chiara, additional, Ruggiero, Eliana, additional, Hamdan, Firas, additional, Feodoroff, Michaela, additional, Antignani, Gabriella, additional, Viitala, Tapani, additional, Pesonen, Sari, additional, Grönholm, Mikaela, additional, Branca, Rui MM, additional, Lehtiö, Janne, additional, and Cerullo, Vincenzo, additional

Published
2022
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17. PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification

Author

Feola, Sara, primary, Haapala, Markus, additional, Peltonen, Karita, additional, Capasso, Cristian, additional, Martins, Beatriz, additional, Antignani, Gabriella, additional, Federico, Antonio, additional, Pietiäinen, Vilja, additional, Chiaro, Jacopo, additional, Feodoroff, Michaela, additional, Russo, Salvatore, additional, Rannikko, Antti, additional, Fusciello, Manlio, additional, Koskela, Satu, additional, Partanen, Jukka, additional, Hamdan, Firas, additional, Tähkä, Sari M., additional, Ylösmäki, Erkko, additional, Greco, Dario, additional, Grönholm, Mikaela, additional, Kekarainen, Tuija, additional, Eshaghi, Masoumeh, additional, Gurvich, Olga L., additional, Ylä-Herttuala, Seppo, additional, M. Branca, Rui M., additional, Lehtiö, Janne, additional, Sikanen, Tiina M., additional, and Cerullo, Vincenzo, additional

Published
2021
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18. Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids

Author

Hamdan, Firas, primary, Ylösmäki, Erkko, additional, Chiaro, Jacopo, additional, Giannoula, Yvonne, additional, Long, Maeve, additional, Fusciello, Manlio, additional, Feola, Sara, additional, Martins, Beatriz, additional, Feodoroff, Michaela, additional, Antignani, Gabriella, additional, Russo, Salvatore, additional, Kari, Otto, additional, Lee, Moon Hee, additional, Järvinen, Petrus, additional, Nisen, Harry, additional, Kreutzman, Anna, additional, Leusen, Jeanette, additional, Mustjoki, Satu, additional, McWilliams, Thomas G, additional, Grönholm, Mikaela, additional, and Cerullo, Vincenzo, additional

Published
2021
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20. Abstract 1488: Viral molecular mimicry influences the antitumor immune response in murine and human melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna, additional, Whalley, Thomas, additional, Capasso, Cristian, additional, Feola, Sara, additional, Grönholm, Mikaela, additional, Hamdan, Firas, additional, Peltonen, Karita, additional, Hernberg, Micaela, additional, Mäkelä, Siru, additional, Karhapää, Hanna, additional, Brown, Paul, additional, Martins, Beatriz, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko, additional, Kreutzman, Anna, additional, Mustjoki, Satu, additional, Szomolay, Barbara, additional, and Cerullo, Vincenzo, additional

Published
2021
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21. Abstract 1867: Characterization in patient derived tumor organoids of novel oncolytic adenoviruses expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitors

Author

Hamdan, Firas, primary, Ylösmäki, Erkko, additional, Chiaro, Jacopo, additional, Giannoula, Yvonne, additional, Long, Maeve, additional, Fusciello, Manlio, additional, Feola, Sara, additional, Martins, Beatriz, additional, Feodoroff, Michaela, additional, Antignani, Gabriella, additional, Kari, Otto, additional, Lee, Moon Hee, additional, Järvinen, Petrus, additional, Nisen, Harry, additional, Kreutzman, Anna, additional, Mustjoki, Satu, additional, McWilliams, Thomas G, additional, Grönholm, Mikaela, additional, and Cerullo, Vincenzo, additional

Published
2021
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22. Abstract 1897: PeptiCHIP: A novel microfluidic-based chip platform for tumor antigen landscape identification

Author

Feola, Sara, primary, Happala, Markus, additional, Peltonen, Karita, additional, Capasso, Cristian, additional, Antignani, Gabriella, additional, Federico, Antonio, additional, Pietiäinen, Vilja, additional, Chiaro, Jacopo, additional, Feodoroff, Michaela, additional, Ranniko, Antti, additional, Fusciello, Manlio, additional, Koskela, Satu, additional, Partanen, Jukka, additional, Hamdan, Firas, additional, Tähkä, Sari, additional, Ylösmäki, Erkko, additional, Greco, Dario, additional, Grönholm, Mikaela, additional, Branca, Rui M M, additional, Lehtiö, Janne, additional, Siikanen, Tiina, additional, and Cerullo, Vincenzo, additional

Published
2021
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24. A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Author

Feola, Sara, primary, Chiaro, Jacopo, additional, Martins, Beatriz, additional, Russo, Salvatore, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko, additional, Hamdan, Firas, additional, Feodoroff, Michaela, additional, Antignani, Gabriella, additional, Viitala, Tapani, additional, Pesonen, Sari, additional, Grönholm, Mikaela, additional, Branca, Rui M M, additional, Lehtiö, Janne, additional, and Cerullo, Vincenzo, additional

Published
2021
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26. Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna H.E., additional, Whalley, Thomas, additional, Capasso, Cristian, additional, Grönholm, Mikaela, additional, Feola, Sara, additional, Peltonen, Karita, additional, Hamdan, Firas, additional, Hernberg, Micaela, additional, Mäkelä, Siru, additional, Karhapää, Hanna, additional, Brown, Paul E., additional, Martins, Beatriz, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko O., additional, Greco, Dario, additional, Kreutzman, Anna S., additional, Mustjoki, Satu, additional, Szomolay, Barbara, additional, and Cerullo, Vincenzo, additional

Published
2021
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27. Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids

Author

Hamdan, Firas, Ylösmäki, Erkko, Chiaro, Jacopo, Giannoula, Yvonne, Long, Maeve, Fusciello, Manlio, Feola, Sara, Martins, Beatriz, Feodoroff, Michaela, Antignani, Gabriella, Russo, Salvatore, Kari, Otto, Lee, Moon, Järvinen, Petrus, Nisen, Harry, Kreutzman, Anna, Leusen, Jeanette, Mustjoki, Satu, McWilliams, Thomas G., Grönholm, Mikaela, Cerullo, Vincenzo, Hamdan, F., Ylosmaki, E., Chiaro, J., Giannoula, Y., Long, M., Fusciello, M., Feola, S., Martins, B., Feodoroff, M., Antignani, G., Russo, S., Kari, O., Lee, M., Jarvinen, P., Nisen, H., Kreutzman, A., Leusen, J., Mustjoki, S., Mcwilliams, T. G., Gronholm, M., Cerullo, V., Division of Pharmaceutical Biosciences, Drug Research Program, ImmunoViroTherapy Lab, Drug Delivery, TRIMM - Translational Immunology Research Program, STEMM - Stem Cells and Metabolism Research Program, Department of Anatomy, Medicum, Institute for Molecular Medicine Finland, Research Services, Drug Delivery Unit, HUS Abdominal Center, HUSLAB, HUS Comprehensive Cancer Center, Department of Clinical Chemistry and Hematology, Digital Precision Cancer Medicine (iCAN), Research Programs Unit, Faculty of Medicine, and Biosciences

Subjects
Organoid, BLOCKADE, Immune Checkpoint Inhibitor, 3122 Cancers, Oncolytic Viruse, GAMMA-RS, Mice, SCID, Receptors, Fc, THERAPY, Adenoviridae, Mice, Mice, Inbred NOD, Cell Line, Tumor, NEUTROPHILS, Oncolytic Virotherapy, RECEPTOR, Animal, EFFICACY, antibody formation, CANCER, Immunoglobulin A, ANTIBODY, 317 Pharmacy, REPLICATION, T-CELLS, 1182 Biochemistry, cell and molecular biology, Neoplasm, Female, Immunotherapy, Human
Abstract

Background Despite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated effector mechanisms. However, these effector mechanisms are inhibited or reduced due to toxicity issues since PD-L1 is not confined to the tumor and also expressed on healthy cells. To increase efficacy while minimizing toxicity, we designed an oncolytic adenovirus that secretes a cross-hybrid Fc-fusion peptide against PD-L1 able to elicit effector mechanisms of an IgG1 and also IgA1 consequently activating neutrophils, a population neglected by IgG1, in order to combine multiple effector mechanisms. Methods The cross-hybrid Fc-fusion peptide comprises of an Fc with the constant domains of an IgA1 and IgG1 which is connected to a PD-1 ectodomain via a GGGS linker and was cloned into an oncolytic adenovirus. We demonstrated that the oncolytic adenovirus was able to secrete the cross-hybrid Fc-fusion peptide able to bind to PD-L1 and activate multiple immune components enhancing tumor cytotoxicity in various cancer cell lines, in vivo and ex vivo renal-cell carcinoma patient-derived organoids. Results Using various techniques to measure cytotoxicity, the cross-hybrid Fc-fusion peptide expressed by the oncolytic adenovirus was shown to activate Fc-effector mechanisms of an IgA1 (neutrophil activation) as well as of an IgG1 (natural killer and complement activation). The activation of multiple effector mechanism simultaneously led to significantly increased tumor killing compared with FDA-approved PD-L1 checkpoint inhibitor (Atezolizumab), IgG1-PDL1 and IgA-PDL1 in various in vitro cell lines, in vivo models and ex vivo renal cell carcinoma organoids. Moreover, in vivo data demonstrated that Ad-Cab did not require CD8+ T cells, unlike conventional checkpoint inhibitors, since it was able to activate other effector populations. Conclusion Arming PD-L1 checkpoint inhibitors with Fc-effector mechanisms of both an IgA1 and an IgG1 can increase efficacy while maintaining safety by limiting expression to the tumor using oncolytic adenovirus. The increase in tumor killing is mostly attributed to the activation of multiple effector populations rather than activating a single effector population leading to significantly higher tumor killing.

Published
2021

28. Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids

Author

CTI Leusen, Infection & Immunity, Cancer, Hamdan, Firas, Ylösmäki, Erkko, Chiaro, Jacopo, Giannoula, Yvonne, Long, Maeve, Fusciello, Manlio, Feola, Sara, Martins, Beatriz, Feodoroff, Michaela, Antignani, Gabriella, Russo, Salvatore, Kari, Otto, Lee, Moon, Järvinen, Petrus, Nisen, Harry, Kreutzman, Anna, Leusen, Jeanette, Mustjoki, Satu, McWilliams, Thomas G, Grönholm, Mikaela, Cerullo, Vincenzo, CTI Leusen, Infection & Immunity, Cancer, Hamdan, Firas, Ylösmäki, Erkko, Chiaro, Jacopo, Giannoula, Yvonne, Long, Maeve, Fusciello, Manlio, Feola, Sara, Martins, Beatriz, Feodoroff, Michaela, Antignani, Gabriella, Russo, Salvatore, Kari, Otto, Lee, Moon, Järvinen, Petrus, Nisen, Harry, Kreutzman, Anna, Leusen, Jeanette, Mustjoki, Satu, McWilliams, Thomas G, Grönholm, Mikaela, and Cerullo, Vincenzo

Published
2021

29. PeptiCHIP: a novel microfluidic-based chip platform for tumour antigen landscape identification

Author

Feola, Sara, primary, Haapala, Markus, additional, Peltonen, Karita, additional, Capasso, Cristian, additional, Martins, Beatriz, additional, Antignani, Gabriella, additional, Federico, Antonio, additional, Pietiäinen, Vilja, additional, Chiaro, Jacopo, additional, Feodoroff, Michaela, additional, Rannikko, Antti, additional, Fusciello, Manlio, additional, Koskela, Satu, additional, Partanen, Jukka, additional, Hamdan, Firas, additional, Tähkä, Sari, additional, Ylösmäki, Erkko, additional, Greco, Dario, additional, Grönholm, Mikaela, additional, Kekarainen, Tuija, additional, Eshaghi, Masoumeh, additional, Gurvich, Olga L., additional, Ylä-Herttuala, Seppo, additional, Branca, Rui Mamede, additional, Lehtiö, Janne, additional, Sikanen, Tiina, additional, and Cerullo, Vincenzo, additional

Published
2021
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30. GAMER-Ad: a novel and rapid method for generating recombinant adenoviruses

Author

Hamdan, Firas, primary, Martins, Beatriz, additional, Feodoroff, Michaela, additional, Giannoula, Yvonne, additional, Feola, Sara, additional, Fusciello, Manlio, additional, Chiaro, Jacopo, additional, Antignani, Gabriella, additional, Grönholm, Mikaela, additional, Ylösmäki, Erkko, additional, and Cerullo, Vincenzo, additional

Published
2021
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31. GAMER-Ad: a novel and rapid method for generating recombinant adenoviruses

Author

Hamdan, Firas, Martins, Beatriz, Feodoroff, Michaela, Giannoula, Yvonne, Feola, Sara, Fusciello, Manlio, Chiaro, Jacopo, Antignani, Gabriella, Grönholm, Mikaela, Ylösmäki, Erkko, and Cerullo, Vincenzo

Subjects
molecular cloning, lcsh:Genetics, lcsh:QH426-470, lcsh:Cytology, adenoviruses, oncolytic viruses, Original Article, lcsh:QH573-671, Gibson Assembly, gene therapy
Abstract

Oncolytic adenoviruses have become ideal agents in the path toward treating cancer. Such viruses have been engineered to conditionally replicate in malignant cells in which certain signaling pathways have been disrupted. Other than such oncolytic properties, the viruses need to activate the immune system in order to sustain a long-term response. Therefore, oncolytic adenoviruses have been genetically modified to express various immune-stimulatory agents to achieve this. However, genetically modifying adenoviruses is very time consuming and labor intensive with the current available methods. In this paper, we describe a novel method we have called GAMER-Ad to genetically modify adenovirus genomes within 2 days. Our method entails the replacement of the gp19k gene in the E3 region with any given gene of interest (GOI) using Gibson Assembly avoiding the homologous recombination between the shuttle and the parental plasmid. In this manuscript as proof of concept we constructed and characterized three oncolytic adenoviruses expressing CXCL9, CXCL10, and interleukin-15 (IL-15). We demonstrate that our novel method is fast, reliable, and simple compared to other methods. We anticipate that our method will be used in the future to genetically engineer oncolytic but also other adenoviruses used for gene therapy as well., Graphical Abstract, GAMER-Ad is a novel method describing how to engineer adenovirus platforms to express any gene of interest in just 2 days for gene therapy or oncolytic purposes. It consists in using the well-described cloning method Gibson Assembly to replace the gp19k region with a gene of interest.

Published
2020

32. Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, Kasanen, Henna H.E., Whalley, Thomas, Capasso, Cristian, Grönholm, Mikaela, Feola, Sara, Peltonen, Karita, Hamdan, Firas, Hernberg, Micaela, Mäkelä, Siru, Karhapää, Hanna, Brown, Paul E., Martins, Beatriz, Fusciello, Manlio, Ylösmäki, Erkko O., Greco, Dario, Kreutzman, Anna S., Mustjoki, Satu, Szomolay, Barbara, Cerullo, Vincenzo, Tampere University, and BioMediTech

Subjects
Mice, Cell Line, Tumor, Molecular Mimicry, Immunity, Animals, Humans, Female, 3111 Biomedicine, Immunotherapy, Melanoma
Abstract

Molecular mimicry is one of the leading mechanisms by which infectious agents can induce autoimmunity. Whether a similar mechanism triggers an antitumor immune response is unexplored, and the role of antiviral T cells infiltrating the tumor has remained anecdotal. To address these questions, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes. Using peptides identified by this tool, we demonstrated that, in mice, preexisting immunity toward specific viral epitopes enhanced the efficacy of cancer immunotherapy via molecular mimicry in different settings. To understand whether this mechanism could partly explain immunotherapy responsiveness in humans, we analyzed a cohort of patients with melanoma undergoing anti-PD1 treatment who had a high IgG titer for cytomegalovirus (CMV). In this cohort of patients, we showed that high levels of CMV-specific antibodies were associated with prolonged progression-free survival and found that, in some cases, peripheral blood mononuclear cells (PBMC) could cross-react with both melanoma and CMV homologous peptides. Finally, T-cell receptor sequencing revealed expansion of the same CD8þ T-cell clones when PBMCs were expanded with tumor or homologous viral peptides. In conclusion, we have demonstrated that preexisting immunity and molecular mimicry could influence the response to immunotherapies. In addition, we have developed a free online tool that can identify tumor antigens and neoantigens highly similar to pathogen antigens to exploit molecular mimicry and cross-reactive T cells in cancer vaccine development. publishedVersion

Published
2020

34. Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma

Author

Chiaro, Jacopo, primary, Kasanen, Henna H. E., additional, Whalley, Thomas, additional, Capasso, Cristian, additional, Grönholm, Mikaela, additional, Feola, Sara, additional, Peltonen, Karita D., additional, Hamdan, Firas S., additional, Hernberg, Micaela M., additional, Mäkelä, Siru, additional, Karhapää, Hanna, additional, Brown, Paul E., additional, Martins, Beatriz, additional, Fusciello, Manlio, additional, Ylösmäki, Erkko, additional, Kreutzman, Anna S., additional, Mustjoki, Satu M., additional, Szomolay, Barbara, additional, and Cerullo, Vincenzo, additional

Published
2020
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35. Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy

Author

Tähtinen, Siri, primary, Feola, Sara, additional, Capasso, Cristian, additional, Laustio, Netta, additional, Groeneveldt, Christianne, additional, Ylösmäki, Erkko O., additional, Ylösmäki, Leena, additional, Martins, Beatriz, additional, Fusciello, Manlio, additional, Medeot, Marta, additional, Tagliamonte, Maria, additional, Chiaro, Jacopo, additional, Hamdan, Firas, additional, Peltonen, Karita, additional, Ranki, Tuuli, additional, Buonaguro, Luigi, additional, and Cerullo, Vincenzo, additional

Published
2020
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38. Circulating microRNAs as biomarkers for early diagnosis of cutaneous melanoma.

Author

Carpi, Sara, Polini, Beatrice, Fogli, Stefano, Podestà, Adriano, Ylösmäki, Erkko, Cerullo, Vincenzo, Romanini, Antonella, and Nieri, Paola

Abstract

Introduction: Cutaneous melanoma is the deadliest form of skin cancer, with a dramatic increase in the incidence rate worldwide over the past decade. Early detection has been shown to improve the outcome of melanoma patients. The identification of noninvasive biomarkers able to identify melanoma at an early stage remains an unmet clinical need. Circulating miRNAs (c-miRNAs), small non-coding RNAs, appear as potential ideal candidate biomarkers due to their stability in biological fluids and easy detectability. Moreover, c-miRNAs are reported to be heavily deregulated in cancer patients. Areas covered: This review examines evidence of the specific c-miRNAs or panels of c-miRNAs reported to be useful in discriminating melanoma from benign cutaneous lesions. Expert opinion: Although the interesting reported by published studies, the non-homogeneity of detection and normalization methods prevents the individuation of single c-miRNA or panel of c-miRNAs that are specific for early detection of cutaneous melanoma. In the future, prospective wide and well-designed clinical trials will be needed to validate the diagnostic potential of some of the c-miRNA candidates in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Personalized Cancer Vaccine Platform for Clinically Relevant Oncolytic Enveloped Viruses

Author

Ylösmäki, Erkko, primary, Malorzo, Cristina, additional, Capasso, Cristian, additional, Honkasalo, Oona, additional, Fusciello, Manlio, additional, Martins, Beatriz, additional, Ylösmäki, Leena, additional, Louna, Antti, additional, Feola, Sara, additional, Paavilainen, Henrik, additional, Peltonen, Karita, additional, Hukkanen, Veijo, additional, Viitala, Tapani, additional, and Cerullo, Vincenzo, additional

Published
2018
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40. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Ager, Casey, Reilley, Matthew, Nicholas, Courtney, Bartkowiak, Todd, Jaiswal, Ashvin, Curran, Michael, Albershardt, Tina C., Bajaj, Anshika, Archer, Jacob F., Reeves, Rebecca S., Ngo, Lisa Y., Berglund, Peter, ter Meulen, Jan, Denis, Caroline, Ghadially, Hormas, Arnoux, Thomas, Chanuc, Fabien, Fuseri, Nicolas, Wilkinson, Robert W., Wagtmann, Nicolai, Morel, Yannis, Andre, Pascale, Atkins, Michael B., Carlino, Matteo S., Ribas, Antoni, Thompson, John A., Choueiri, Toni K., Hodi, F. Stephen, Hwu, Wen-Jen, McDermott, David F., Atkinson, Victoria, Cebon, Jonathan S., Fitzharris, Bernie, Jameson, Michael B., McNeil, Catriona, Hill, Andrew G., Mangin, Eric, Ahamadi, Malidi, van Vugt, Marianne, van Zutphen, Mariëlle, Ibrahim, Nageatte, Long, Georgina V., Gartrell, Robyn, Blake, Zoe, Simoes, Ines, Fu, Yichun, Saito, Takuro, Qian, Yingzhi, Lu, Yan, Saenger, Yvonne M., Budhu, Sadna, De Henau, Olivier, Zappasodi, Roberta, Schlunegger, Kyle, Freimark, Bruce, Hutchins, Jeff, Barker, Christopher A., Wolchok, Jedd D., Merghoub, Taha, Burova, Elena, Allbritton, Omaira, Hong, Peter, Dai, Jie, Pei, Jerry, Liu, Matt, Kantrowitz, Joel, Lai, Venus, Poueymirou, William, MacDonald, Douglas, Ioffe, Ella, Mohrs, Markus, Olson, William, Thurston, Gavin, Capasso, Cristian, Frascaro, Federica, Carpi, Sara, Tähtinen, Siri, Feola, Sara, Fusciello, Manlio, Peltonen, Karita, Martins, Beatriz, Sjöberg, Madeleine, Pesonen, Sari, Ranki, Tuuli, Kyruk, Lukasz, Ylösmäki, Erkko, Cerullo, Vincenzo, Cerignoli, Fabio, Xi, Biao, Guenther, Garret, Yu, Naichen, Muir, Lincoln, Zhao, Leyna, Abassi, Yama, Cervera-Carrascón, Víctor, Siurala, Mikko, Santos, João, Havunen, Riikka, Parviainen, Suvi, Hemminki, Akseli, Dalgleish, Angus, Mudan, Satvinder, DeBenedette, Mark, Plachco, Ana, Gamble, Alicia, Grogan, Elizabeth W., Krisko, John, Tcherepanova, Irina, Nicolette, Charles, Dhupkar, Pooja, Yu, Ling, Kleinerman, Eugenie S., Gordon, Nancy, Grenga, Italia, Lepone, Lauren, Gameiro, Sofia, Knudson, Karin M., Fantini, Massimo, Tsang, Kwong, Hodge, James, Donahue, Renee, Schlom, Jeffrey, Evans, Elizabeth, Bussler, Holm, Mallow, Crystal, Reilly, Christine, Torno, Sebold, Scrivens, Maria, Foster, Cathie, Howell, Alan, Balch, Leslie, Knapp, Alyssa, Leonard, John E., Paris, Mark, Fisher, Terry, Hu-Lieskovan, Siwen, Smith, Ernest, Zauderer, Maurice, Fogler, William, Franklin, Marilyn, Thayer, Matt, Saims, Dan, Magnani, John L., Gong, Jian, Gray, Michael, Fromm, George, de Silva, Suresh, Giffin, Louise, Xu, Xin, Rose, Jason, Schreiber, Taylor H., Gameiro, Sofia R., Clavijo, Paul E., Allen, Clint T., Hodge, James W., Tsang, Kwong Y., Grogan, Jane, Manieri, Nicholas, Chiang, Eugene, Caplazi, Patrick, Yadav, Mahesh, Hagner, Patrick, Chiu, Hsiling, Waldman, Michelle, Klippel, Anke, Thakurta, Anjan, Pourdehnad, Michael, Gandhi, Anita, Henrich, Ian, Quick, Laura, Young, Rob, Chou, Margaret, Hotson, Andrew, Willingham, Stephen, Ho, Po, Choy, Carmen, Laport, Ginna, McCaffery, Ian, Miller, Richard, Tipton, Kimberly A., Wong, Kenneth R., Singson, Victoria, Wong, Chihunt, Chan, Chanty, Huang, Yuanhiu, Liu, Shouchun, Richardson, Jennifer H., Kavanaugh, W. Michael, West, James, Irving, Bryan A., Jaini, Ritika, Loya, Matthew, Eng, Charis, Johnson, Melissa L., Adjei, Alex A., Opyrchal, Mateusz, Ramalingam, Suresh, Janne, Pasi A., Dominguez, George, Gabrilovich, Dmitry, de Leon, Laura, Hasapidis, Jeannette, Diede, Scott J., Ordentlich, Peter, Cruickshank, Scott, Meyers, Michael L., Hellmann, Matthew D., Kalinski, Pawel, Zureikat, Amer, Edwards, Robert, Muthuswamy, Ravi, Obermajer, Nataša, Urban, Julie, Butterfield, Lisa H., Gooding, William, Zeh, Herbert, Bartlett, David, Zubkova, Olga, Agapova, Larissa, Kapralova, Marina, Krasovskaia, Liudmila, Ovsepyan, Armen, Lykov, Maxim, Eremeev, Artem, Bokovanov, Vladimir, Grigoryeva, Olga, Karpov, Andrey, Ruchko, Sergey, Shuster, Alexandr, Khalil, Danny N., Campesato, Luis Felipe, Li, Yanyun, Lazorchak, Adam S., Patterson, Troy D., Ding, Yueyun, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Gowda, Nagaraj, Ramachandra, Raghuveer, Samiulla, Dodheri, Giri, Sanjeev, Eswarappa, Rajesh, Ramachandra, Murali, Tuck, David, Wyant, Timothy, Leshem, Jasmin, Liu, Xiu-fen, Bera, Tapan, Terabe, Masaki, Bossenmaier, Birgit, Niederfellner, Gerhard, Reiter, Yoram, Pastan, Ira, Xia, Leiming, Xia, Yang, Hu, Yangyang, Wang, Yi, Bao, Yangyi, Dai, Fu, Huang, Shiang, Hurt, Elaine, Hollingsworth, Robert E., Lum, Lawrence G., Chang, Alfred E., Wicha, Max S., Li, Qiao, Mace, Thomas, Makhijani, Neil, Talbert, Erin, Young, Gregory, Guttridge, Denis, Conwell, Darwin, Lesinski, Gregory B., Gonzales, Rodney JM Macedo, Huffman, Austin P., Wang, Ximi K., Reshef, Ran, MacKinnon, Andy, Chen, Jason, Gross, Matt, Marguier, Gisele, Shwonek, Peter, Sotirovska, Natalija, Steggerda, Susanne, Parlati, Francesco, Makkouk, Amani, Bennett, Mark K., Emberley, Ethan, Huang, Tony, Li, Weiqun, Neou, Silinda, Pan, Alison, Zhang, Jing, Zhang, Winter, Marshall, Netonia, Marron, Thomas U., Agudo, Judith, Brown, Brian, Brody, Joshua, McQuinn, Christopher, Farren, Matthew, Komar, Hannah, Shakya, Reena, Ludwug, Thomas, Morillon, Y. Maurice, Hammond, Scott A., Greiner, John W., Nath, Pulak R., Schwartz, Anthony L., Maric, Dragan, Roberts, David D., Naing, Aung, Papadopoulos, Kyriakos P., Autio, Karen A., Wong, Deborah J., Patel, Manish, Falchook, Gerald, Pant, Shubham, Ott, Patrick A., Whiteside, Melinda, Patnaik, Amita, Mumm, John, Janku, Filip, Chan, Ivan, Bauer, Todd, Colen, Rivka, VanVlasselaer, Peter, Brown, Gail L., Tannir, Nizar M., Oft, Martin, Infante, Jeffrey, Lipson, Evan, Gopal, Ajay, Neelapu, Sattva S., Armand, Philippe, Spurgeon, Stephen, Leonard, John P., Sanborn, Rachel E., Melero, Ignacio, Gajewski, Thomas F., Maurer, Matthew, Perna, Serena, Gutierrez, Andres A., Clynes, Raphael, Mitra, Priyam, Suryawanshi, Satyendra, Gladstone, Douglas, Callahan, Margaret K., Crooks, James, Brown, Sheila, Gauthier, Audrey, de Boisferon, Marc Hillairet, MacDonald, Andrew, Brunet, Laura Rosa, Rothwell, William T., Bell, Peter, Wilson, James M., Sato-Kaneko, Fumi, Yao, Shiyin, Zhang, Shannon S., Carson, Dennis A., Guiducci, Cristina, Coffman, Robert L., Kitaura, Kazutaka, Matsutani, Takaji, Suzuki, Ryuji, Hayashi, Tomoko, Cohen, Ezra E. W., Schaer, David, Li, Yanxia, Dobkin, Julie, Amatulli, Michael, Hall, Gerald, Doman, Thompson, Manro, Jason, Dorsey, Frank Charles, Sams, Lillian, Holmgaard, Rikke, Persaud, Krishnadatt, Ludwig, Dale, Surguladze, David, Kauh, John S., Novosiadly, Ruslan, Kalos, Michael, Driscoll, Kyla, Pandha, Hardev, Ralph, Christy, Harrington, Kevin, Curti, Brendan, Akerley, Wallace, Gupta, Sumati, Melcher, Alan, Mansfield, David, Kaufman, David R., Schmidt, Emmett, Grose, Mark, Davies, Bronwyn, Karpathy, Roberta, Shafren, Darren, Shamalov, Katerina, Cohen, Cyrille, Sharma, Naveen, Allison, James, Shekarian, Tala, Valsesia-Wittmann, Sandrine, Caux, Christophe, Marabelle, Aurelien, Slomovitz, Brian M., Moore, Kathleen M., Youssoufian, Hagop, Posner, Marshall, Tewary, Poonam, Brooks, Alan D., Xu, Ya-Ming, Wijeratne, Kithsiri, Gunatilaka, Leslie A. A., Sayers, Thomas J., Vasilakos, John P., Alston, Tesha, Dovedi, Simon, Elvecrog, James, Grigsby, Iwen, Herbst, Ronald, Johnson, Karen, Moeckly, Craig, Mullins, Stefanie, Siebenaler, Kristen, SternJohn, Julius, Tilahun, Ashenafi, Tomai, Mark A., Vogel, Katharina, Vietsch, Eveline E., Wellstein, Anton, Wythes, Martin, Crosignani, Stefano, Tumang, Joseph, Alekar, Shilpa, Bingham, Patrick, Cauwenberghs, Sandra, Chaplin, Jenny, Dalvie, Deepak, Denies, Sofie, De Maeseneire, Coraline, Feng, JunLi, Frederix, Kim, Greasley, Samantha, Guo, Jie, Hardwick, James, Kaiser, Stephen, Jessen, Katti, Kindt, Erick, Letellier, Marie-Claire, Li, Wenlin, Maegley, Karen, Marillier, Reece, Miller, Nichol, Murray, Brion, Pirson, Romain, Preillon, Julie, Rabolli, Virginie, Ray, Chad, Ryan, Kevin, Scales, Stephanie, Srirangam, Jay, Solowiej, Jim, Stewart, Al, Streiner, Nicole, Torti, Vince, Tsaparikos, Konstantinos, Zheng, Xianxian, Driessens, Gregory, Gomes, Bruno, Kraus, Manfred, Xu, Chunxiao, Zhang, Yanping, Kradjian, Giorgio, Qin, Guozhong, Qi, Jin, Xu, Xiaomei, Marelli, Bo, Yu, Huakui, Guzman, Wilson, Tighe, Rober, Salazar, Rachel, Lo, Kin-Ming, English, Jessie, Radvanyi, Laszlo, Lan, Yan, Postow, Michael, Senbabaoglu, Yasin, Gasmi, Billel, Zhong, Hong, Liu, Cailian, Hirschhorhn-Cymerman, Daniel, Zha, Yuanyuan, Malnassy, Gregory, Fulton, Noreen, Park, Jae-Hyun, Stock, Wendy, Nakamura, Yusuke, Liu, Hongtao, Ju, Xiaoming, Kosoff, Rachelle, Ramos, Kimberly, Coder, Brandon, Petit, Robert, Princiotta, Michael, Perry, Kyle, Zou, Jun, Arina, Ainhoa, Fernandez, Christian, Zheng, Wenxin, Beckett, Michael A., Mauceri, Helena J., Fu, Yang-Xin, Weichselbaum, Ralph R., Lewis, Whitney, Han, Yanyan, Wu, Yeting, Yang, Chou, Huang, Jing, Wu, Dongyun, Li, Jin, Liang, Xiaoling, Zhou, Xiangjun, Hou, Jinlin, Hassan, Raffit, Jahan, Thierry, Antonia, Scott J., Kindler, Hedy L., Alley, Evan W., Honarmand, Somayeh, Liu, Weiqun, Leong, Meredith L., Whiting, Chan C., Nair, Nitya, Enstrom, Amanda, Lemmens, Edward E., Tsujikawa, Takahiro, Kumar, Sushil, Coussens, Lisa M., Murphy, Aimee L., Brockstedt, Dirk G., Koch, Sven D., Sebastian, Martin, Weiss, Christian, Früh, Martin, Pless, Miklos, Cathomas, Richard, Hilbe, Wolfgang, Pall, Georg, Wehler, Thomas, Alt, Jürgen, Bischoff, Helge, Geissler, Michael, Griesinger, Frank, Kollmeier, Jens, Papachristofilou, Alexandros, Doener, Fatma, Fotin-Mleczek, Mariola, Hipp, Madeleine, Hong, Henoch S., Kallen, Karl-Josef, Klinkhardt, Ute, Stosnach, Claudia, Scheel, Birgit, Schroeder, Andreas, Seibel, Tobias, Gnad-Vogt, Ulrike, Zippelius, Alfred, Park, Ha-Ram, Ahn, Yong-Oon, Kim, Tae Min, Kim, Soyeon, Kim, Seulki, Lee, Yu Soo, Keam, Bhumsuk, Kim, Dong-Wan, Heo, Dae Seog, Pilon-Thomas, Shari, Weber, Amy, Morse, Jennifer, Kodumudi, Krithika, Liu, Hao, Mullinax, John, Sarnaik, Amod A., Pike, Luke, Bang, Andrew, Balboni, Tracy, Taylor, Allison, Spektor, Alexander, Wilhite, Tyler, Krishnan, Monica, Cagney, Daniel, Alexander, Brian, Aizer, Ayal, Buchbinder, Elizabeth, Awad, Mark, Ghandi, Leena, Schoenfeld, Jonathan, Lessey-Morillon, Elizabeth, Ridnour, Lisa, Segal, Neil H., Sharma, Manish, Le, Dung T., Ferris, Robert L., Zelenetz, Andrew D., Levy, Ronald, Lossos, Izidore S., Jacobson, Caron, Ramchandren, Radhakrishnan, Godwin, John, Colevas, A. Dimitrios, Meier, Roland, Krishnan, Suba, Gu, Xuemin, Neely, Jaclyn, Timmerman, John, Vanpouille-Box, Claire I., Formenti, Silvia C., Demaria, Sandra, Wennerberg, Erik, Mediero, Aranzazu, Cronstein, Bruce N., Gustafson, Michael P., DiCostanzo, AriCeli, Wheatley, Courtney, Kim, Chul-Ho, Bornschlegl, Svetlana, Gastineau, Dennis A., Johnson, Bruce D., Dietz, Allan B., MacDonald, Cameron, Bucsek, Mark, Qiao, Guanxi, Hylander, Bonnie, Repasky, Elizabeth, Turbitt, William J., Xu, Yitong, Mastro, Andrea, Rogers, Connie J., Withers, Sita, Wang, Ziming, Khuat, Lam T., Dunai, Cordelia, Blazar, Bruce R., Longo, Dan, Rebhun, Robert, Grossenbacher, Steven K., Monjazeb, Arta, Murphy, William J., Rowlinson, Scott, Agnello, Giulia, Alters, Susan, Lowe, David, Scharping, Nicole, Menk, Ashley V., Whetstone, Ryan, Zeng, Xue, Delgoffe, Greg M., Santos, Patricia M., Shi, Jian, Delgoffe, Greg, Nagasaka, Misako, Sukari, Ammar, Byrne-Steele, Miranda, Pan, Wenjing, Hou, Xiaohong, Brown, Brittany, Eisenhower, Mary, Han, Jian, Collins, Natalie, Manguso, Robert, Pope, Hans, Shrestha, Yashaswi, Boehm, Jesse, Haining, W. Nicholas, Cron, Kyle R., Sivan, Ayelet, Aquino-Michaels, Keston, Orecchioni, Marco, Bedognetti, Davide, Hendrickx, Wouter, Fuoco, Claudia, Spada, Filomena, Sgarrella, Francesco, Cesareni, Gianni, Marincola, Francesco, Kostarelos, Kostas, Bianco, Alberto, Delogu, Lucia, Roelands, Jessica, Boughorbel, Sabri, Decock, Julie, Presnell, Scott, Wang, Ena, Marincola, Franco M., Kuppen, Peter, Ceccarelli, Michele, Rinchai, Darawan, Chaussabel, Damien, Miller, Lance, Nguyen, Andrew, Sanborn, J. Zachary, Vaske, Charles, Rabizadeh, Shahrooz, Niazi, Kayvan, Benz, Steven, Patel, Shashank, Restifo, Nicholas, White, James, Angiuoli, Sam, Sausen, Mark, Jones, Sian, Sevdali, Maria, Simmons, John, Velculescu, Victor, Diaz, Luis, Zhang, Theresa, Sims, Jennifer S., Barton, Sunjay M., Kadenhe-Chiweshe, Angela, Dela Cruz, Filemon, Turk, Andrew T., Mazzeo, Christopher F., Kung, Andrew L., Bruce, Jeffrey N., Yamashiro, Darrell J., Connolly, Eileen P., Baird, Jason, Crittenden, Marka, Friedman, David, Xiao, Hong, Leidner, Rom, Bell, Bryan, Young, Kristina, Gough, Michael, Bian, Zhen, Kidder, Koby, Liu, Yuan, Curran, Emily, Chen, Xiufen, Corrales, Leticia P., Kline, Justin, Aguilar, Ethan G., Guerriero, Jennifer, Sotayo, Alaba, Ponichtera, Holly, Pourzia, Alexandra, Schad, Sara, Carrasco, Ruben, Lazo, Suzan, Bronson, Roderick, Letai, Anthony, Kornbluth, Richard S., Gupta, Sachin, Termini, James, Guirado, Elizabeth, Stone, Geoffrey W., Meyer, Christina, Helming, Laura, Wilson, Nicholas, Hofmeister, Robert, Neubert, Natalie J., Tillé, Laure, Barras, David, Soneson, Charlotte, Baumgaertner, Petra, Rimoldi, Donata, Gfeller, David, Delorenzi, Mauro, Fuertes Marraco, Silvia A., Speiser, Daniel E., Abraham, Tara S., Xiang, Bo, Magee, Michael S., Waldman, Scott A., Snook, Adam E., Blogowski, Wojciech, Zuba-Surma, Ewa, Budkowska, Marta, Salata, Daria, Dolegowska, Barbara, Starzynska, Teresa, Chan, Leo, Somanchi, Srinivas, McCulley, Kelsey, Lee, Dean, Buettner, Nico, Shi, Feng, Myers, Paisley T., Curbishley, Stuart, Penny, Sarah A., Steadman, Lora, Millar, David, Speers, Ellen, Ruth, Nicola, Wong, Gabriel, Thimme, Robert, Adams, David, Cobbold, Mark, Thomas, Remy, Al-Muftah, Mariam, Wong, Michael KK, Morse, Michael, Clark, Joseph I., Kaufman, Howard L., Daniels, Gregory A., Hua, Hong, Rao, Tharak, Dutcher, Janice P., Kang, Kai, Saunthararajah, Yogen, Velcheti, Vamsidhar, Kumar, Vikas, Anwar, Firoz, Verma, Amita, Chheda, Zinal, Kohanbash, Gary, Sidney, John, Okada, Kaori, Shrivastav, Shruti, Carrera, Diego A., Liu, Shuming, Jahan, Naznin, Mueller, Sabine, Pollack, Ian F., Carcaboso, Angel M., Sette, Alessandro, Hou, Yafei, Okada, Hideho, Field, Jessica J., Zeng, Weiping, Shih, Vincent FS, Law, Che-Leung, Senter, Peter D., Gardai, Shyra J., Okeley, Nicole M., Abelin, Jennifer G., Saeed, Abu Z., Malaker, Stacy A., Shabanowitz, Jeffrey, Ward, Stephen T., Hunt, Donald F., Profusek, Pam, Wood, Laura, Shepard, Dale, Grivas, Petros, Kapp, Kerstin, Volz, Barbara, Oswald, Detlef, Wittig, Burghardt, Schmidt, Manuel, Sefrin, Julian P., Hillringhaus, Lars, Lifke, Valeria, Lifke, Alexander, Skaletskaya, Anna, Ponte, Jose, Chittenden, Thomas, Setiady, Yulius, Sivado, Eva, Thomas, Vincent, El Alaoui, Meddy, Papot, Sébastien, Dumontet, Charles, Dyson, Mike, McCafferty, John, El Alaoui, Said, Bommareddy, Praveen K., Zloza, Andrew, Kohlhapp, Frederick, Silk, Ann W., Jhawar, Sachin, Paneque, Tomas, Newman, Jenna, Beltran, Pedro, Cao, Felicia, Hong, Bang-Xing, Rodriguez-Cruz, Tania, Song, Xiao-Tong, Gottschalk, Stephen, Calderon, Hugo, Illingworth, Sam, Brown, Alice, Fisher, Kerry, Seymour, Len, Champion, Brian, Eriksson, Emma, Wenthe, Jessica, Hellström, Ann-Charlotte, Paul-Wetterberg, Gabriella, Loskog, Angelica, Milenova, Ioanna, Ståhle, Magnus, Jarblad-Leja, Justyna, Ullenhag, Gustav, Dimberg, Anna, Moreno, Rafael, Alemany, Ramon, Goyal, Sharad, Silk, Ann, Mehnert, Janice, Gabrail, Nashat, Bryan, Jennifer, Medina, Daniel, Mitchell, Leah, Yagiz, Kader, Lopez, Fernando, Mendoza, Daniel, Munday, Anthony, Gruber, Harry, Jolly, Douglas, Fuhrmann, Steven, Radoja, Sasa, Tan, Wei, Pourchet, Aldo, Frey, Alan, Mohr, Ian, Mulvey, Matthew, Andtbacka, Robert H. I., Ross, Merrick, Agarwala, Sanjiv, Grossmann, Kenneth, Taylor, Matthew, Vetto, John, Neves, Rogerio, Daud, Adil, Khong, Hung, Meek, Stephanie M., Ungerleider, Richard, Welden, Scott, Tanaka, Maki, Williams, Matthew, Hallmeyer, Sigrun, Fox, Bernard, Feng, Zipei, Paustian, Christopher, Bifulco, Carlo, Zafar, Sadia, Hemminki, Otto, Bramante, Simona, Vassilev, Lotta, Wang, Hongjie, Lieber, Andre, Hemmi, Silvio, de Gruijl, Tanja, Kanerva, Anna, Ansari, Tameem, Sundararaman, Srividya, Roen, Diana, Lehmann, Paul, Bloom, Anja C., Bender, Lewis H., Walters, Ian B., Berzofsky, Jay A., Chapelin, Fanny, Ahrens, Eric T., DeFalco, Jeff, Harbell, Michael, Manning-Bog, Amy, Scholz, Alexander, Zhang, Danhui, Baia, Gilson, Tan, Yann Chong, Sokolove, Jeremy, Kim, Dongkyoon, Williamson, Kevin, Chen, Xiaomu, Colrain, Jillian, Santo, Gregg Espiritu, Nguyen, Ngan, Volkmuth, Wayne, Greenberg, Norman, Robinson, William, Emerling, Daniel, Drake, Charles G., Petrylak, Daniel P., Antonarakis, Emmanuel S., Kibel, Adam S., Chang, Nancy N., Vu, Tuyen, Campogan, Dwayne, Haynes, Heather, Trager, James B., Sheikh, Nadeem A., Quinn, David I., Kirk, Peter, Addepalli, Murali, Chang, Thomas, Zhang, Ping, Konakova, Marina, Hagihara, Katsunobu, Pai, Steven, VanderVeen, Laurie, Obalapur, Palakshi, Kuo, Peiwen, Quach, Phi, Fong, Lawrence, Charych, Deborah H., Zalevsky, Jonathan, Langowski, John L., Kirksey, Yolanda, Nutakki, Ravi, Kolarkar, Shalini, Pena, Rhoneil, Hoch, Ute, Doberstein, Stephen K., Cha, John, Mallon, Zach, Perez, Myra, McDaniel, Amanda, Anand, Snjezana, Uecker, Darrin, Nuccitelli, Richard, Wieckowski, Eva, Muthuswamy, Ravikumar, Ravindranathan, Roshni, Renrick, Ariana N., Thounaojam, Menaka, Thomas, Portia, Pellom, Samuel, Shanker, Anil, Dudimah, Duafalia, Brooks, Alan, Su, Yu-Lin, Adamus, Tomasz, Zhang, Qifang, Nechaev, Sergey, Kortylewski, Marcin, Wei, Spencer, Anderson, Clark, Tang, Chad, Schoenhals, Jonathan, Tsouko, Efrosini, Heymach, John, de Groot, Patricia, Chang, Joe, Hess, Kenneth R., Diab, Adi, Sharma, Padmanee, Hong, David, Welsh, James, Parsons, Andrea J., Leleux, Jardin, Ascarateil, Stephane, Koziol, Marie Eve, Bai, Dina, Dai, Peihong, Wang, Weiyi, Yang, Ning, Shuman, Stewart, Deng, Liang, Dillon, Patrick, Petroni, Gina, Brenin, David, Bullock, Kim, Olson, Walter, Smolkin, Mark E., Smith, Kelly, Nail, Carmel, Slingluff, Craig L., Sharma, Meenu, Fa’ak, Faisal, Janssen, Louise, Khong, Hiep, Xiao, Zhilan, Hailemichael, Yared, Singh, Manisha, Vianden, Christina, Overwijk, Willem W., Facciabene, Andrea, Stefano, Pierini, Chongyung, Fang, Rafail, Stavros, Nielsen, Michael, Vanderslice, Peter, Woodside, Darren G., Market, Robert V., Biediger, Ronald J., Marathi, Upendra K., Hollevoet, Kevin, Geukens, Nick, Declerck, Paul, Joly, Nathalie, McIntosh, Laura, Paramithiotis, Eustache, Rizell, Magnus, Sternby, Malin, Andersson, Bengt, Karlsson-Parra, Alex, Kuai, Rui, Ochyl, Lukasz, Schwendeman, Anna, Moon, James, Deng, Weiwen, Hudson, Thomas E., Hanson, Bill, Rae, Chris S., Burrill, Joel, Skoble, Justin, Katibah, George, deVries, Michele, Lauer, Peter, Dubensky, Thomas W., Chen, Xin, Zhou, Li, Ren, Xiubao, Aggarwal, Charu, Mangrolia, Drishty, Cohen, Roger, Weinstein, Gregory, Morrow, Matthew, Bauml, Joshua, Kraynyak, Kim, Boyer, Jean, Yan, Jian, Lee, Jessica, Humeau, Laurent, Oyola, Sandra, Duff, Susan, Weiner, David, Yang, Zane, Bagarazzi, Mark, McNeel, Douglas G., Eickhoff, Jens, Jeraj, Robert, Staab, Mary Jane, Straus, Jane, Rekoske, Brian, Liu, Glenn, Melssen, Marit, Grosh, William, Varhegyi, Nikole, Galeassi, Nadejda, Deacon, Donna H., Gaughan, Elizabeth, Ghisoli, Maurizio, Barve, Minal, Mennel, Robert, Wallraven, Gladice, Manning, Luisa, Senzer, Neil, Nemunaitis, John, Ogasawara, Masahiro, Ota, Shuichi, Peace, Kaitlin M., Hale, Diane F., Vreeland, Timothy J., Jackson, Doreen O., Berry, John S., Trappey, Alfred F., Herbert, Garth S., Clifton, Guy T., Hardin, Mark O., Toms, Anne, Qiao, Na, Litton, Jennifer, Peoples, George E., Mittendorf, Elizabeth A., Ghamsari, Lila, Flano, Emilio, Jacques, Judy, Liu, Biao, Havel, Jonathan, Makarov, Vladimir, Chan, Timothy A., Flechtner, Jessica B., Facciponte, John, Ugel, Stefano, De Sanctis, Francesco, Coukos, George, Paris, Sébastien, Pottier, Agnes, Levy, Laurent, Lu, Bo, Cappuccini, Federica, Pollock, Emily, Bryant, Richard, Hamdy, Freddie, Hill, Adrian, Redchenko, Irina, Sultan, Hussein, Kumai, Takumi, Fesenkova, Valentyna, Celis, Esteban, Fernando, Ingrid, Palena, Claudia, David, Justin M., Gabitzsch, Elizabeth, Jones, Frank, Gulley, James L., Herranz, Mireia Uribe, Wada, Hiroshi, Shimizu, Atsushi, Osada, Toshihiro, Fukaya, Satoshi, Sasaki, Eiji, Abolhalaj, Milad, Askmyr, David, Lundberg, Kristina, Albrekt, Ann-Sofie, Greiff, Lennart, Lindstedt, Malin, Flies, Dallas B., Higuchi, Tomoe, Ornatowski, Wojciech, Harris, Jaryse, Adams, Sarah F., Aguilera, Todd, Rafat, Marjan, Castellini, Laura, Shehade, Hussein, Kariolis, Mihalis, Jang, Dadi, vonEbyen, Rie, Graves, Edward, Ellies, Lesley, Rankin, Erinn, Koong, Albert, Giaccia, Amato, Ajina, Reham, Wang, Shangzi, Smith, Jill, Pierobon, Mariaelena, Jablonski, Sandra, Petricoin, Emanuel, Weiner, Louis M., Sherry, Lorcan, Waller, John, Anderson, Mark, Bigley, Alison, Bernatchez, Chantale, Haymaker, Cara, Kluger, Harriet, Tetzlaff, Michael, Jackson, Natalie, Gergel, Ivan, Tagliaferri, Mary, Hwu, Patrick, Snzol, Mario, Hurwitz, Michael, Barberi, Theresa, Martin, Allison, Suresh, Rahul, Barakat, David, Harris-Bookman, Sarah, Drake, Charles, Friedman, Alan, Berkey, Sara, Downs-Canner, Stephanie, Edwards, Robert P., Curiel, Tyler, Odunsi, Kunle, Bruno, Tullia C., Moore, Brandon, Squalls, Olivia, Ebner, Peggy, Waugh, Katherine, Mitchell, John, Franklin, Wilbur, Merrick, Daniel, McCarter, Martin, Palmer, Brent, Kern, Jeffrey, Vignali, Dario, Slansky, Jill, Chan, Anissa S. H., Qiu, Xiaohong, Fraser, Kathryn, Jonas, Adria, Ottoson, Nadine, Gordon, Keith, Kangas, Takashi O., Leonardo, Steven, Ertelt, Kathleen, Walsh, Richard, Uhlik, Mark, Graff, Jeremy, Bose, Nandita, Gupta, Ravi, Mandloi, Nitin, Paul, Kiran, Patil, Ashwini, Sathian, Rekha, Mohan, Aparna, Manoharan, Malini, Chaudhuri, Amitabha, Chen, Yu, Lin, Jing, Ye, Yun-bin, Xu, Chun-wei, Chen, Gang, Guo, Zeng-qing, Komarov, Andrey, Chenchik, Alex, Makhanov, Michael, Frangou, Costa, Zheng, Yi, Coltharp, Carla, Unfricht, Darryn, Dilworth, Ryan, Fridman, Leticia, Liu, Linying, Rajopadhye, Milind, Miller, Peter, Concha-Benavente, Fernando, Bauman, Julie, Trivedi, Sumita, Srivastava, Raghvendra, Ohr, James, Heron, Dwight, Duvvuri, Uma, Kim, Seungwon, Torrey, Heather, Mera, Toshi, Okubo, Yoshiaki, Vanamee, Eva, Foster, Rosemary, Faustman, Denise, Stack, Edward, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Marks, Douglas, Taback, Bret, Horst, Basil, Glickman, Laura Hix, Kanne, David B., Gauthier, Kelsey S., Desbien, Anthony L., Francica, Brian, Leong, Justin L., Sung, Leonard, Metchette, Ken, Kasibhatla, Shailaja, Pferdekamper, Anne Marie, Zheng, Lianxing, Cho, Charles, Feng, Yan, McKenna, Jeffery M., Tallarico, John, Bender, Steven, Ndubaku, Chudi, McWhirter, Sarah M., Gugel, Elena Gonzalez, Bell, Charles J. M., Munk, Adiel, Muniz, Luciana, Bhardwaj, Nina, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scholler, Nathalie, Yin, Catherine, Van der Meijs, Pien, Prantner, Andrew M., Krejsa, Cecile M., Smith, Leia, Johnson, Brian, Branstetter, Daniel, Stein, Paul L., Jaen, Juan C., Tan, Joanne BL, Chen, Ada, Park, Timothy, Powers, Jay P., Sexton, Holly, Xu, Guifen, Young, Steve W., Schindler, Ulrike, Deng, Wentao, Klinke, David John, Komar, Hannah M., Serpa, Gregory, Elnaggar, Omar, Hart, Philip, Schmidt, Carl, Dillhoff, Mary, Jin, Ming, Ostrowski, Michael C., Koti, Madhuri, Au, Katrina, Peterson, Nichole, Truesdell, Peter, Reid-Schachter, Gillian, Graham, Charles, Craig, Andrew, Francis, Julie-Ann, Kotlan, Beatrix, Balatoni, Timea, Farkas, Emil, Toth, Laszlo, Ujhelyi, Mihaly, Savolt, Akos, Doleschall, Zoltan, Horvath, Szabolcs, Eles, Klara, Olasz, Judit, Csuka, Orsolya, Kasler, Miklos, Liszkay, Gabriella, Barnea, Eytan, Blakely, Collin, Flynn, Patrick, Goodman, Reid, Bueno, Raphael, Sugarbaker, David, Jablons, David, Broaddus, V. Courtney, West, Brian, Kunk, Paul R., Obeid, Joseph M., Winters, Kevin, Pramoonjago, Patcharin, Stelow, Edward B., Bauer, Todd W., Rahma, Osama E., Lamble, Adam, Kosaka, Yoko, Huang, Fei, Saser, Kate A., Adams, Homer, Tognon, Christina E., Laderas, Ted, McWeeney, Shannon, Loriaux, Marc, Tyner, Jeffery W., Druker, Brian J., Lind, Evan F., Liu, Zhuqing, Lu, Shanhong, Kane, Lawrence P., Shayan, Gulidanna, Femel, Julia, Lane, Ryan, Booth, Jamie, Lund, Amanda W., Rodriguez, Anthony, Engelhard, Victor H., Metelli, Alessandra, Wu, Bill X., Fugle, Caroline W., Saleh, Rachidi, Sun, Shaoli, Wu, Jennifer, Liu, Bei, Li, Zihai, Morris, Zachary S., Guy, Emily I., Heinze, Clinton, Kler, Jasdeep, Gressett, Monica M., Werner, Lauryn R., Gillies, Stephen D., Korman, Alan J., Loibner, Hans, Hank, Jacquelyn A., Rakhmilevich, Alexander L., Harari, Paul M., Sondel, Paul M., Huelsmann, Erica, Broucek, Joseph, Brech, Dorothee, Straub, Tobias, Irmler, Martin, Beckers, Johannes, Buettner, Florian, Schaeffeler, Elke, Schwab, Matthias, Noessner, Elfriede, Wolfreys, Alison, Da Costa, Andre, Silva, John, Crosby, Andrea, Staelens, Ludovicus, Craggs, Graham, Cauvin, Annick, Mason, Sean, Paterson, Alison M., Lake, Andrew C., Armet, Caroline M., O’Connor, Rachel W., Hill, Jonathan A., Normant, Emmanuel, Adam, Ammar, Biniszkiewicz, Detlev M., Chappel, Scott C., Palombella, Vito J., Holland, Pamela M., Becker, Annette, Leleti, Manmohan R., Newcomb, Eric, Tan, Joanne B. L., Rapisuwon, Suthee, Radfar, Arash, Gardner, Kellie, Gibney, Geoffrey, Atkins, Michael, Rennier, Keith R., Crowder, Robert, Wang, Ping, Pachynski, Russell K., Carrero, Rosa M. Santana, Rivas, Sarai, Beceren-Braun, Figen, Anthony, Scott, Schluns, Kimberly S., Sawant, Deepali, Chikina, Maria, Yano, Hiroshi, Workman, Creg, Salerno, Elise, Mauldin, Ileana, Deacon, Donna, Shea, Sofia, Pinczewski, Joel, Gajewski, Thomas, Spranger, Stefani, Horton, Brendan, Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Puri, Raj K., Sweis, Randy F., Bao, Riyue, Luke, Jason, Theodoraki, Marie-Nicole, Mogundo, Frances-Mary, Won, Haejung, Moreira, Dayson, Gao, Chan, Zhao, Xingli, Duttagupta, Priyanka, Jones, Jeremy, D’Apuzzo, Massimo, and Pal, Sumanta

Subjects
Meeting Abstracts
Published
2016

42. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Ager, Casey, primary, Reilley, Matthew, additional, Nicholas, Courtney, additional, Bartkowiak, Todd, additional, Jaiswal, Ashvin, additional, Curran, Michael, additional, Albershardt, Tina C., additional, Bajaj, Anshika, additional, Archer, Jacob F., additional, Reeves, Rebecca S., additional, Ngo, Lisa Y., additional, Berglund, Peter, additional, ter Meulen, Jan, additional, Denis, Caroline, additional, Ghadially, Hormas, additional, Arnoux, Thomas, additional, Chanuc, Fabien, additional, Fuseri, Nicolas, additional, Wilkinson, Robert W., additional, Wagtmann, Nicolai, additional, Morel, Yannis, additional, Andre, Pascale, additional, Atkins, Michael B., additional, Carlino, Matteo S., additional, Ribas, Antoni, additional, Thompson, John A., additional, Choueiri, Toni K., additional, Hodi, F. Stephen, additional, Hwu, Wen-Jen, additional, McDermott, David F., additional, Atkinson, Victoria, additional, Cebon, Jonathan S., additional, Fitzharris, Bernie, additional, Jameson, Michael B., additional, McNeil, Catriona, additional, Hill, Andrew G., additional, Mangin, Eric, additional, Ahamadi, Malidi, additional, van Vugt, Marianne, additional, van Zutphen, Mariëlle, additional, Ibrahim, Nageatte, additional, Long, Georgina V., additional, Gartrell, Robyn, additional, Blake, Zoe, additional, Simoes, Ines, additional, Fu, Yichun, additional, Saito, Takuro, additional, Qian, Yingzhi, additional, Lu, Yan, additional, Saenger, Yvonne M., additional, Budhu, Sadna, additional, De Henau, Olivier, additional, Zappasodi, Roberta, additional, Schlunegger, Kyle, additional, Freimark, Bruce, additional, Hutchins, Jeff, additional, Barker, Christopher A., additional, Wolchok, Jedd D., additional, Merghoub, Taha, additional, Burova, Elena, additional, Allbritton, Omaira, additional, Hong, Peter, additional, Dai, Jie, additional, Pei, Jerry, additional, Liu, Matt, additional, Kantrowitz, Joel, additional, Lai, Venus, additional, Poueymirou, William, additional, MacDonald, Douglas, additional, Ioffe, Ella, additional, Mohrs, Markus, additional, Olson, William, additional, Thurston, Gavin, additional, Capasso, Cristian, additional, Frascaro, Federica, additional, Carpi, Sara, additional, Tähtinen, Siri, additional, Feola, Sara, additional, Fusciello, Manlio, additional, Peltonen, Karita, additional, Martins, Beatriz, additional, Sjöberg, Madeleine, additional, Pesonen, Sari, additional, Ranki, Tuuli, additional, Kyruk, Lukasz, additional, Ylösmäki, Erkko, additional, Cerullo, Vincenzo, additional, Cerignoli, Fabio, additional, Xi, Biao, additional, Guenther, Garret, additional, Yu, Naichen, additional, Muir, Lincoln, additional, Zhao, Leyna, additional, Abassi, Yama, additional, Cervera-Carrascón, Víctor, additional, Siurala, Mikko, additional, Santos, João, additional, Havunen, Riikka, additional, Parviainen, Suvi, additional, Hemminki, Akseli, additional, Dalgleish, Angus, additional, Mudan, Satvinder, additional, DeBenedette, Mark, additional, Plachco, Ana, additional, Gamble, Alicia, additional, Grogan, Elizabeth W., additional, Krisko, John, additional, Tcherepanova, Irina, additional, Nicolette, Charles, additional, Dhupkar, Pooja, additional, Yu, Ling, additional, Kleinerman, Eugenie S., additional, Gordon, Nancy, additional, Grenga, Italia, additional, Lepone, Lauren, additional, Gameiro, Sofia, additional, Knudson, Karin M., additional, Fantini, Massimo, additional, Tsang, Kwong, additional, Hodge, James, additional, Donahue, Renee, additional, Schlom, Jeffrey, additional, Evans, Elizabeth, additional, Bussler, Holm, additional, Mallow, Crystal, additional, Reilly, Christine, additional, Torno, Sebold, additional, Scrivens, Maria, additional, Foster, Cathie, additional, Howell, Alan, additional, Balch, Leslie, additional, Knapp, Alyssa, additional, Leonard, John E., additional, Paris, Mark, additional, Fisher, Terry, additional, Hu-Lieskovan, Siwen, additional, Smith, Ernest, additional, Zauderer, Maurice, additional, Fogler, William, additional, Franklin, Marilyn, additional, Thayer, Matt, additional, Saims, Dan, additional, Magnani, John L., additional, Gong, Jian, additional, Gray, Michael, additional, Fromm, George, additional, de Silva, Suresh, additional, Giffin, Louise, additional, Xu, Xin, additional, Rose, Jason, additional, Schreiber, Taylor H., additional, Gameiro, Sofia R., additional, Clavijo, Paul E., additional, Allen, Clint T., additional, Hodge, James W., additional, Tsang, Kwong Y., additional, Grogan, Jane, additional, Manieri, Nicholas, additional, Chiang, Eugene, additional, Caplazi, Patrick, additional, Yadav, Mahesh, additional, Hagner, Patrick, additional, Chiu, Hsiling, additional, Waldman, Michelle, additional, Klippel, Anke, additional, Thakurta, Anjan, additional, Pourdehnad, Michael, additional, Gandhi, Anita, additional, Henrich, Ian, additional, Quick, Laura, additional, Young, Rob, additional, Chou, Margaret, additional, Hotson, Andrew, additional, Willingham, Stephen, additional, Ho, Po, additional, Choy, Carmen, additional, Laport, Ginna, additional, McCaffery, Ian, additional, Miller, Richard, additional, Tipton, Kimberly A., additional, Wong, Kenneth R., additional, Singson, Victoria, additional, Wong, Chihunt, additional, Chan, Chanty, additional, Huang, Yuanhiu, additional, Liu, Shouchun, additional, Richardson, Jennifer H., additional, Kavanaugh, W. Michael, additional, West, James, additional, Irving, Bryan A., additional, Jaini, Ritika, additional, Loya, Matthew, additional, Eng, Charis, additional, Johnson, Melissa L., additional, Adjei, Alex A., additional, Opyrchal, Mateusz, additional, Ramalingam, Suresh, additional, Janne, Pasi A., additional, Dominguez, George, additional, Gabrilovich, Dmitry, additional, de Leon, Laura, additional, Hasapidis, Jeannette, additional, Diede, Scott J., additional, Ordentlich, Peter, additional, Cruickshank, Scott, additional, Meyers, Michael L., additional, Hellmann, Matthew D., additional, Kalinski, Pawel, additional, Zureikat, Amer, additional, Edwards, Robert, additional, Muthuswamy, Ravi, additional, Obermajer, Nataša, additional, Urban, Julie, additional, Butterfield, Lisa H., additional, Gooding, William, additional, Zeh, Herbert, additional, Bartlett, David, additional, Zubkova, Olga, additional, Agapova, Larissa, additional, Kapralova, Marina, additional, Krasovskaia, Liudmila, additional, Ovsepyan, Armen, additional, Lykov, Maxim, additional, Eremeev, Artem, additional, Bokovanov, Vladimir, additional, Grigoryeva, Olga, additional, Karpov, Andrey, additional, Ruchko, Sergey, additional, Shuster, Alexandr, additional, Khalil, Danny N., additional, Campesato, Luis Felipe, additional, Li, Yanyun, additional, Lazorchak, Adam S., additional, Patterson, Troy D., additional, Ding, Yueyun, additional, Sasikumar, Pottayil, additional, Sudarshan, Naremaddepalli, additional, Gowda, Nagaraj, additional, Ramachandra, Raghuveer, additional, Samiulla, Dodheri, additional, Giri, Sanjeev, additional, Eswarappa, Rajesh, additional, Ramachandra, Murali, additional, Tuck, David, additional, Wyant, Timothy, additional, Leshem, Jasmin, additional, Liu, Xiu-fen, additional, Bera, Tapan, additional, Terabe, Masaki, additional, Bossenmaier, Birgit, additional, Niederfellner, Gerhard, additional, Reiter, Yoram, additional, Pastan, Ira, additional, Xia, Leiming, additional, Xia, Yang, additional, Hu, Yangyang, additional, Wang, Yi, additional, Bao, Yangyi, additional, Dai, Fu, additional, Huang, Shiang, additional, Hurt, Elaine, additional, Hollingsworth, Robert E., additional, Lum, Lawrence G., additional, Chang, Alfred E., additional, Wicha, Max S., additional, Li, Qiao, additional, Mace, Thomas, additional, Makhijani, Neil, additional, Talbert, Erin, additional, Young, Gregory, additional, Guttridge, Denis, additional, Conwell, Darwin, additional, Lesinski, Gregory B., additional, Gonzales, Rodney JM Macedo, additional, Huffman, Austin P., additional, Wang, Ximi K., additional, Reshef, Ran, additional, MacKinnon, Andy, additional, Chen, Jason, additional, Gross, Matt, additional, Marguier, Gisele, additional, Shwonek, Peter, additional, Sotirovska, Natalija, additional, Steggerda, Susanne, additional, Parlati, Francesco, additional, Makkouk, Amani, additional, Bennett, Mark K., additional, Emberley, Ethan, additional, Huang, Tony, additional, Li, Weiqun, additional, Neou, Silinda, additional, Pan, Alison, additional, Zhang, Jing, additional, Zhang, Winter, additional, Marshall, Netonia, additional, Marron, Thomas U., additional, Agudo, Judith, additional, Brown, Brian, additional, Brody, Joshua, additional, McQuinn, Christopher, additional, Farren, Matthew, additional, Komar, Hannah, additional, Shakya, Reena, additional, Ludwug, Thomas, additional, Morillon, Y. Maurice, additional, Hammond, Scott A., additional, Greiner, John W., additional, Nath, Pulak R., additional, Schwartz, Anthony L., additional, Maric, Dragan, additional, Roberts, David D., additional, Naing, Aung, additional, Papadopoulos, Kyriakos P., additional, Autio, Karen A., additional, Wong, Deborah J., additional, Patel, Manish, additional, Falchook, Gerald, additional, Pant, Shubham, additional, Ott, Patrick A., additional, Whiteside, Melinda, additional, Patnaik, Amita, additional, Mumm, John, additional, Janku, Filip, additional, Chan, Ivan, additional, Bauer, Todd, additional, Colen, Rivka, additional, VanVlasselaer, Peter, additional, Brown, Gail L., additional, Tannir, Nizar M., additional, Oft, Martin, additional, Infante, Jeffrey, additional, Lipson, Evan, additional, Gopal, Ajay, additional, Neelapu, Sattva S., additional, Armand, Philippe, additional, Spurgeon, Stephen, additional, Leonard, John P., additional, Sanborn, Rachel E., additional, Melero, Ignacio, additional, Gajewski, Thomas F., additional, Maurer, Matthew, additional, Perna, Serena, additional, Gutierrez, Andres A., additional, Clynes, Raphael, additional, Mitra, Priyam, additional, Suryawanshi, Satyendra, additional, Gladstone, Douglas, additional, Callahan, Margaret K., additional, Crooks, James, additional, Brown, Sheila, additional, Gauthier, Audrey, additional, de Boisferon, Marc Hillairet, additional, MacDonald, Andrew, additional, Brunet, Laura Rosa, additional, Rothwell, William T., additional, Bell, Peter, additional, Wilson, James M., additional, Sato-Kaneko, Fumi, additional, Yao, Shiyin, additional, Zhang, Shannon S., additional, Carson, Dennis A., additional, Guiducci, Cristina, additional, Coffman, Robert L., additional, Kitaura, Kazutaka, additional, Matsutani, Takaji, additional, Suzuki, Ryuji, additional, Hayashi, Tomoko, additional, Cohen, Ezra E. W., additional, Schaer, David, additional, Li, Yanxia, additional, Dobkin, Julie, additional, Amatulli, Michael, additional, Hall, Gerald, additional, Doman, Thompson, additional, Manro, Jason, additional, Dorsey, Frank Charles, additional, Sams, Lillian, additional, Holmgaard, Rikke, additional, Persaud, Krishnadatt, additional, Ludwig, Dale, additional, Surguladze, David, additional, Kauh, John S., additional, Novosiadly, Ruslan, additional, Kalos, Michael, additional, Driscoll, Kyla, additional, Pandha, Hardev, additional, Ralph, Christy, additional, Harrington, Kevin, additional, Curti, Brendan, additional, Akerley, Wallace, additional, Gupta, Sumati, additional, Melcher, Alan, additional, Mansfield, David, additional, Kaufman, David R., additional, Schmidt, Emmett, additional, Grose, Mark, additional, Davies, Bronwyn, additional, Karpathy, Roberta, additional, Shafren, Darren, additional, Shamalov, Katerina, additional, Cohen, Cyrille, additional, Sharma, Naveen, additional, Allison, James, additional, Shekarian, Tala, additional, Valsesia-Wittmann, Sandrine, additional, Caux, Christophe, additional, Marabelle, Aurelien, additional, Slomovitz, Brian M., additional, Moore, Kathleen M., additional, Youssoufian, Hagop, additional, Posner, Marshall, additional, Tewary, Poonam, additional, Brooks, Alan D., additional, Xu, Ya-Ming, additional, Wijeratne, Kithsiri, additional, Gunatilaka, Leslie A. A., additional, Sayers, Thomas J., additional, Vasilakos, John P., additional, Alston, Tesha, additional, Dovedi, Simon, additional, Elvecrog, James, additional, Grigsby, Iwen, additional, Herbst, Ronald, additional, Johnson, Karen, additional, Moeckly, Craig, additional, Mullins, Stefanie, additional, Siebenaler, Kristen, additional, SternJohn, Julius, additional, Tilahun, Ashenafi, additional, Tomai, Mark A., additional, Vogel, Katharina, additional, Vietsch, Eveline E., additional, Wellstein, Anton, additional, Wythes, Martin, additional, Crosignani, Stefano, additional, Tumang, Joseph, additional, Alekar, Shilpa, additional, Bingham, Patrick, additional, Cauwenberghs, Sandra, additional, Chaplin, Jenny, additional, Dalvie, Deepak, additional, Denies, Sofie, additional, De Maeseneire, Coraline, additional, Feng, JunLi, additional, Frederix, Kim, additional, Greasley, Samantha, additional, Guo, Jie, additional, Hardwick, James, additional, Kaiser, Stephen, additional, Jessen, Katti, additional, Kindt, Erick, additional, Letellier, Marie-Claire, additional, Li, Wenlin, additional, Maegley, Karen, additional, Marillier, Reece, additional, Miller, Nichol, additional, Murray, Brion, additional, Pirson, Romain, additional, Preillon, Julie, additional, Rabolli, Virginie, additional, Ray, Chad, additional, Ryan, Kevin, additional, Scales, Stephanie, additional, Srirangam, Jay, additional, Solowiej, Jim, additional, Stewart, Al, additional, Streiner, Nicole, additional, Torti, Vince, additional, Tsaparikos, Konstantinos, additional, Zheng, Xianxian, additional, Driessens, Gregory, additional, Gomes, Bruno, additional, Kraus, Manfred, additional, Xu, Chunxiao, additional, Zhang, Yanping, additional, Kradjian, Giorgio, additional, Qin, Guozhong, additional, Qi, Jin, additional, Xu, Xiaomei, additional, Marelli, Bo, additional, Yu, Huakui, additional, Guzman, Wilson, additional, Tighe, Rober, additional, Salazar, Rachel, additional, Lo, Kin-Ming, additional, English, Jessie, additional, Radvanyi, Laszlo, additional, Lan, Yan, additional, Postow, Michael, additional, Senbabaoglu, Yasin, additional, Gasmi, Billel, additional, Zhong, Hong, additional, Liu, Cailian, additional, Hirschhorhn-Cymerman, Daniel, additional, Zha, Yuanyuan, additional, Malnassy, Gregory, additional, Fulton, Noreen, additional, Park, Jae-Hyun, additional, Stock, Wendy, additional, Nakamura, Yusuke, additional, Liu, Hongtao, additional, Ju, Xiaoming, additional, Kosoff, Rachelle, additional, Ramos, Kimberly, additional, Coder, Brandon, additional, Petit, Robert, additional, Princiotta, Michael, additional, Perry, Kyle, additional, Zou, Jun, additional, Arina, Ainhoa, additional, Fernandez, Christian, additional, Zheng, Wenxin, additional, Beckett, Michael A., additional, Mauceri, Helena J., additional, Fu, Yang-Xin, additional, Weichselbaum, Ralph R., additional, Lewis, Whitney, additional, Han, Yanyan, additional, Wu, Yeting, additional, Yang, Chou, additional, Huang, Jing, additional, Wu, Dongyun, additional, Li, Jin, additional, Liang, Xiaoling, additional, Zhou, Xiangjun, additional, Hou, Jinlin, additional, Hassan, Raffit, additional, Jahan, Thierry, additional, Antonia, Scott J., additional, Kindler, Hedy L., additional, Alley, Evan W., additional, Honarmand, Somayeh, additional, Liu, Weiqun, additional, Leong, Meredith L., additional, Whiting, Chan C., additional, Nair, Nitya, additional, Enstrom, Amanda, additional, Lemmens, Edward E., additional, Tsujikawa, Takahiro, additional, Kumar, Sushil, additional, Coussens, Lisa M., additional, Murphy, Aimee L., additional, Brockstedt, Dirk G., additional, Koch, Sven D., additional, Sebastian, Martin, additional, Weiss, Christian, additional, Früh, Martin, additional, Pless, Miklos, additional, Cathomas, Richard, additional, Hilbe, Wolfgang, additional, Pall, Georg, additional, Wehler, Thomas, additional, Alt, Jürgen, additional, Bischoff, Helge, additional, Geissler, Michael, additional, Griesinger, Frank, additional, Kollmeier, Jens, additional, Papachristofilou, Alexandros, additional, Doener, Fatma, additional, Fotin-Mleczek, Mariola, additional, Hipp, Madeleine, additional, Hong, Henoch S., additional, Kallen, Karl-Josef, additional, Klinkhardt, Ute, additional, Stosnach, Claudia, additional, Scheel, Birgit, additional, Schroeder, Andreas, additional, Seibel, Tobias, additional, Gnad-Vogt, Ulrike, additional, Zippelius, Alfred, additional, Park, Ha-Ram, additional, Ahn, Yong-Oon, additional, Kim, Tae Min, additional, Kim, Soyeon, additional, Kim, Seulki, additional, Lee, Yu Soo, additional, Keam, Bhumsuk, additional, Kim, Dong-Wan, additional, Heo, Dae Seog, additional, Pilon-Thomas, Shari, additional, Weber, Amy, additional, Morse, Jennifer, additional, Kodumudi, Krithika, additional, Liu, Hao, additional, Mullinax, John, additional, Sarnaik, Amod A., additional, Pike, Luke, additional, Bang, Andrew, additional, Balboni, Tracy, additional, Taylor, Allison, additional, Spektor, Alexander, additional, Wilhite, Tyler, additional, Krishnan, Monica, additional, Cagney, Daniel, additional, Alexander, Brian, additional, Aizer, Ayal, additional, Buchbinder, Elizabeth, additional, Awad, Mark, additional, Ghandi, Leena, additional, Schoenfeld, Jonathan, additional, Lessey-Morillon, Elizabeth, additional, Ridnour, Lisa, additional, Segal, Neil H., additional, Sharma, Manish, additional, Le, Dung T., additional, Ferris, Robert L., additional, Zelenetz, Andrew D., additional, Levy, Ronald, additional, Lossos, Izidore S., additional, Jacobson, Caron, additional, Ramchandren, Radhakrishnan, additional, Godwin, John, additional, Colevas, A. Dimitrios, additional, Meier, Roland, additional, Krishnan, Suba, additional, Gu, Xuemin, additional, Neely, Jaclyn, additional, Timmerman, John, additional, Vanpouille-Box, Claire I., additional, Formenti, Silvia C., additional, Demaria, Sandra, additional, Wennerberg, Erik, additional, Mediero, Aranzazu, additional, Cronstein, Bruce N., additional, Gustafson, Michael P., additional, DiCostanzo, AriCeli, additional, Wheatley, Courtney, additional, Kim, Chul-Ho, additional, Bornschlegl, Svetlana, additional, Gastineau, Dennis A., additional, Johnson, Bruce D., additional, Dietz, Allan B., additional, MacDonald, Cameron, additional, Bucsek, Mark, additional, Qiao, Guanxi, additional, Hylander, Bonnie, additional, Repasky, Elizabeth, additional, Turbitt, William J., additional, Xu, Yitong, additional, Mastro, Andrea, additional, Rogers, Connie J., additional, Withers, Sita, additional, Wang, Ziming, additional, Khuat, Lam T., additional, Dunai, Cordelia, additional, Blazar, Bruce R., additional, Longo, Dan, additional, Rebhun, Robert, additional, Grossenbacher, Steven K., additional, Monjazeb, Arta, additional, Murphy, William J., additional, Rowlinson, Scott, additional, Agnello, Giulia, additional, Alters, Susan, additional, Lowe, David, additional, Scharping, Nicole, additional, Menk, Ashley V., additional, Whetstone, Ryan, additional, Zeng, Xue, additional, Delgoffe, Greg M., additional, Santos, Patricia M., additional, Shi, Jian, additional, Delgoffe, Greg, additional, Nagasaka, Misako, additional, Sukari, Ammar, additional, Byrne-Steele, Miranda, additional, Pan, Wenjing, additional, Hou, Xiaohong, additional, Brown, Brittany, additional, Eisenhower, Mary, additional, Han, Jian, additional, Collins, Natalie, additional, Manguso, Robert, additional, Pope, Hans, additional, Shrestha, Yashaswi, additional, Boehm, Jesse, additional, Haining, W. Nicholas, additional, Cron, Kyle R., additional, Sivan, Ayelet, additional, Aquino-Michaels, Keston, additional, Orecchioni, Marco, additional, Bedognetti, Davide, additional, Hendrickx, Wouter, additional, Fuoco, Claudia, additional, Spada, Filomena, additional, Sgarrella, Francesco, additional, Cesareni, Gianni, additional, Marincola, Francesco, additional, Kostarelos, Kostas, additional, Bianco, Alberto, additional, Delogu, Lucia, additional, Roelands, Jessica, additional, Boughorbel, Sabri, additional, Decock, Julie, additional, Presnell, Scott, additional, Wang, Ena, additional, Marincola, Franco M., additional, Kuppen, Peter, additional, Ceccarelli, Michele, additional, Rinchai, Darawan, additional, Chaussabel, Damien, additional, Miller, Lance, additional, Nguyen, Andrew, additional, Sanborn, J. Zachary, additional, Vaske, Charles, additional, Rabizadeh, Shahrooz, additional, Niazi, Kayvan, additional, Benz, Steven, additional, Patel, Shashank, additional, Restifo, Nicholas, additional, White, James, additional, Angiuoli, Sam, additional, Sausen, Mark, additional, Jones, Sian, additional, Sevdali, Maria, additional, Simmons, John, additional, Velculescu, Victor, additional, Diaz, Luis, additional, Zhang, Theresa, additional, Sims, Jennifer S., additional, Barton, Sunjay M., additional, Kadenhe-Chiweshe, Angela, additional, Dela Cruz, Filemon, additional, Turk, Andrew T., additional, Mazzeo, Christopher F., additional, Kung, Andrew L., additional, Bruce, Jeffrey N., additional, Yamashiro, Darrell J., additional, Connolly, Eileen P., additional, Baird, Jason, additional, Crittenden, Marka, additional, Friedman, David, additional, Xiao, Hong, additional, Leidner, Rom, additional, Bell, Bryan, additional, Young, Kristina, additional, Gough, Michael, additional, Bian, Zhen, additional, Kidder, Koby, additional, Liu, Yuan, additional, Curran, Emily, additional, Chen, Xiufen, additional, Corrales, Leticia P., additional, Kline, Justin, additional, Aguilar, Ethan G., additional, Guerriero, Jennifer, additional, Sotayo, Alaba, additional, Ponichtera, Holly, additional, Pourzia, Alexandra, additional, Schad, Sara, additional, Carrasco, Ruben, additional, Lazo, Suzan, additional, Bronson, Roderick, additional, Letai, Anthony, additional, Kornbluth, Richard S., additional, Gupta, Sachin, additional, Termini, James, additional, Guirado, Elizabeth, additional, Stone, Geoffrey W., additional, Meyer, Christina, additional, Helming, Laura, additional, Wilson, Nicholas, additional, Hofmeister, Robert, additional, Neubert, Natalie J., additional, Tillé, Laure, additional, Barras, David, additional, Soneson, Charlotte, additional, Baumgaertner, Petra, additional, Rimoldi, Donata, additional, Gfeller, David, additional, Delorenzi, Mauro, additional, Fuertes Marraco, Silvia A., additional, Speiser, Daniel E., additional, Abraham, Tara S., additional, Xiang, Bo, additional, Magee, Michael S., additional, Waldman, Scott A., additional, Snook, Adam E., additional, Blogowski, Wojciech, additional, Zuba-Surma, Ewa, additional, Budkowska, Marta, additional, Salata, Daria, additional, Dolegowska, Barbara, additional, Starzynska, Teresa, additional, Chan, Leo, additional, Somanchi, Srinivas, additional, McCulley, Kelsey, additional, Lee, Dean, additional, Buettner, Nico, additional, Shi, Feng, additional, Myers, Paisley T., additional, Curbishley, Stuart, additional, Penny, Sarah A., additional, Steadman, Lora, additional, Millar, David, additional, Speers, Ellen, additional, Ruth, Nicola, additional, Wong, Gabriel, additional, Thimme, Robert, additional, Adams, David, additional, Cobbold, Mark, additional, Thomas, Remy, additional, Al-Muftah, Mariam, additional, Wong, Michael KK, additional, Morse, Michael, additional, Clark, Joseph I., additional, Kaufman, Howard L., additional, Daniels, Gregory A., additional, Hua, Hong, additional, Rao, Tharak, additional, Dutcher, Janice P., additional, Kang, Kai, additional, Saunthararajah, Yogen, additional, Velcheti, Vamsidhar, additional, Kumar, Vikas, additional, Anwar, Firoz, additional, Verma, Amita, additional, Chheda, Zinal, additional, Kohanbash, Gary, additional, Sidney, John, additional, Okada, Kaori, additional, Shrivastav, Shruti, additional, Carrera, Diego A., additional, Liu, Shuming, additional, Jahan, Naznin, additional, Mueller, Sabine, additional, Pollack, Ian F., additional, Carcaboso, Angel M., additional, Sette, Alessandro, additional, Hou, Yafei, additional, Okada, Hideho, additional, Field, Jessica J., additional, Zeng, Weiping, additional, Shih, Vincent FS, additional, Law, Che-Leung, additional, Senter, Peter D., additional, Gardai, Shyra J., additional, Okeley, Nicole M., additional, Abelin, Jennifer G., additional, Saeed, Abu Z., additional, Malaker, Stacy A., additional, Shabanowitz, Jeffrey, additional, Ward, Stephen T., additional, Hunt, Donald F., additional, Profusek, Pam, additional, Wood, Laura, additional, Shepard, Dale, additional, Grivas, Petros, additional, Kapp, Kerstin, additional, Volz, Barbara, additional, Oswald, Detlef, additional, Wittig, Burghardt, additional, Schmidt, Manuel, additional, Sefrin, Julian P., additional, Hillringhaus, Lars, additional, Lifke, Valeria, additional, Lifke, Alexander, additional, Skaletskaya, Anna, additional, Ponte, Jose, additional, Chittenden, Thomas, additional, Setiady, Yulius, additional, Sivado, Eva, additional, Thomas, Vincent, additional, El Alaoui, Meddy, additional, Papot, Sébastien, additional, Dumontet, Charles, additional, Dyson, Mike, additional, McCafferty, John, additional, El Alaoui, Said, additional, Bommareddy, Praveen K., additional, Zloza, Andrew, additional, Kohlhapp, Frederick, additional, Silk, Ann W., additional, Jhawar, Sachin, additional, Paneque, Tomas, additional, Newman, Jenna, additional, Beltran, Pedro, additional, Cao, Felicia, additional, Hong, Bang-Xing, additional, Rodriguez-Cruz, Tania, additional, Song, Xiao-Tong, additional, Gottschalk, Stephen, additional, Calderon, Hugo, additional, Illingworth, Sam, additional, Brown, Alice, additional, Fisher, Kerry, additional, Seymour, Len, additional, Champion, Brian, additional, Eriksson, Emma, additional, Wenthe, Jessica, additional, Hellström, Ann-Charlotte, additional, Paul-Wetterberg, Gabriella, additional, Loskog, Angelica, additional, Milenova, Ioanna, additional, Ståhle, Magnus, additional, Jarblad-Leja, Justyna, additional, Ullenhag, Gustav, additional, Dimberg, Anna, additional, Moreno, Rafael, additional, Alemany, Ramon, additional, Goyal, Sharad, additional, Silk, Ann, additional, Mehnert, Janice, additional, Gabrail, Nashat, additional, Bryan, Jennifer, additional, Medina, Daniel, additional, Mitchell, Leah, additional, Yagiz, Kader, additional, Lopez, Fernando, additional, Mendoza, Daniel, additional, Munday, Anthony, additional, Gruber, Harry, additional, Jolly, Douglas, additional, Fuhrmann, Steven, additional, Radoja, Sasa, additional, Tan, Wei, additional, Pourchet, Aldo, additional, Frey, Alan, additional, Mohr, Ian, additional, Mulvey, Matthew, additional, Andtbacka, Robert H. I., additional, Ross, Merrick, additional, Agarwala, Sanjiv, additional, Grossmann, Kenneth, additional, Taylor, Matthew, additional, Vetto, John, additional, Neves, Rogerio, additional, Daud, Adil, additional, Khong, Hung, additional, Meek, Stephanie M., additional, Ungerleider, Richard, additional, Welden, Scott, additional, Tanaka, Maki, additional, Williams, Matthew, additional, Hallmeyer, Sigrun, additional, Fox, Bernard, additional, Feng, Zipei, additional, Paustian, Christopher, additional, Bifulco, Carlo, additional, Zafar, Sadia, additional, Hemminki, Otto, additional, Bramante, Simona, additional, Vassilev, Lotta, additional, Wang, Hongjie, additional, Lieber, Andre, additional, Hemmi, Silvio, additional, de Gruijl, Tanja, additional, Kanerva, Anna, additional, Ansari, Tameem, additional, Sundararaman, Srividya, additional, Roen, Diana, additional, Lehmann, Paul, additional, Bloom, Anja C., additional, Bender, Lewis H., additional, Walters, Ian B., additional, Berzofsky, Jay A., additional, Chapelin, Fanny, additional, Ahrens, Eric T., additional, DeFalco, Jeff, additional, Harbell, Michael, additional, Manning-Bog, Amy, additional, Scholz, Alexander, additional, Zhang, Danhui, additional, Baia, Gilson, additional, Tan, Yann Chong, additional, Sokolove, Jeremy, additional, Kim, Dongkyoon, additional, Williamson, Kevin, additional, Chen, Xiaomu, additional, Colrain, Jillian, additional, Santo, Gregg Espiritu, additional, Nguyen, Ngan, additional, Volkmuth, Wayne, additional, Greenberg, Norman, additional, Robinson, William, additional, Emerling, Daniel, additional, Drake, Charles G., additional, Petrylak, Daniel P., additional, Antonarakis, Emmanuel S., additional, Kibel, Adam S., additional, Chang, Nancy N., additional, Vu, Tuyen, additional, Campogan, Dwayne, additional, Haynes, Heather, additional, Trager, James B., additional, Sheikh, Nadeem A., additional, Quinn, David I., additional, Kirk, Peter, additional, Addepalli, Murali, additional, Chang, Thomas, additional, Zhang, Ping, additional, Konakova, Marina, additional, Hagihara, Katsunobu, additional, Pai, Steven, additional, VanderVeen, Laurie, additional, Obalapur, Palakshi, additional, Kuo, Peiwen, additional, Quach, Phi, additional, Fong, Lawrence, additional, Charych, Deborah H., additional, Zalevsky, Jonathan, additional, Langowski, John L., additional, Kirksey, Yolanda, additional, Nutakki, Ravi, additional, Kolarkar, Shalini, additional, Pena, Rhoneil, additional, Hoch, Ute, additional, Doberstein, Stephen K., additional, Cha, John, additional, Mallon, Zach, additional, Perez, Myra, additional, McDaniel, Amanda, additional, Anand, Snjezana, additional, Uecker, Darrin, additional, Nuccitelli, Richard, additional, Wieckowski, Eva, additional, Muthuswamy, Ravikumar, additional, Ravindranathan, Roshni, additional, Renrick, Ariana N., additional, Thounaojam, Menaka, additional, Thomas, Portia, additional, Pellom, Samuel, additional, Shanker, Anil, additional, Dudimah, Duafalia, additional, Brooks, Alan, additional, Su, Yu-Lin, additional, Adamus, Tomasz, additional, Zhang, Qifang, additional, Nechaev, Sergey, additional, Kortylewski, Marcin, additional, Wei, Spencer, additional, Anderson, Clark, additional, Tang, Chad, additional, Schoenhals, Jonathan, additional, Tsouko, Efrosini, additional, Heymach, John, additional, de Groot, Patricia, additional, Chang, Joe, additional, Hess, Kenneth R., additional, Diab, Adi, additional, Sharma, Padmanee, additional, Hong, David, additional, Welsh, James, additional, Parsons, Andrea J., additional, Leleux, Jardin, additional, Ascarateil, Stephane, additional, Koziol, Marie Eve, additional, Bai, Dina, additional, Dai, Peihong, additional, Wang, Weiyi, additional, Yang, Ning, additional, Shuman, Stewart, additional, Deng, Liang, additional, Dillon, Patrick, additional, Petroni, Gina, additional, Brenin, David, additional, Bullock, Kim, additional, Olson, Walter, additional, Smolkin, Mark E., additional, Smith, Kelly, additional, Nail, Carmel, additional, Slingluff, Craig L., additional, Sharma, Meenu, additional, Fa’ak, Faisal, additional, Janssen, Louise, additional, Khong, Hiep, additional, Xiao, Zhilan, additional, Hailemichael, Yared, additional, Singh, Manisha, additional, Vianden, Christina, additional, Overwijk, Willem W., additional, Facciabene, Andrea, additional, Stefano, Pierini, additional, Chongyung, Fang, additional, Rafail, Stavros, additional, Nielsen, Michael, additional, Vanderslice, Peter, additional, Woodside, Darren G., additional, Market, Robert V., additional, Biediger, Ronald J., additional, Marathi, Upendra K., additional, Hollevoet, Kevin, additional, Geukens, Nick, additional, Declerck, Paul, additional, Joly, Nathalie, additional, McIntosh, Laura, additional, Paramithiotis, Eustache, additional, Rizell, Magnus, additional, Sternby, Malin, additional, Andersson, Bengt, additional, Karlsson-Parra, Alex, additional, Kuai, Rui, additional, Ochyl, Lukasz, additional, Schwendeman, Anna, additional, Moon, James, additional, Deng, Weiwen, additional, Hudson, Thomas E., additional, Hanson, Bill, additional, Rae, Chris S., additional, Burrill, Joel, additional, Skoble, Justin, additional, Katibah, George, additional, deVries, Michele, additional, Lauer, Peter, additional, Dubensky, Thomas W., additional, Chen, Xin, additional, Zhou, Li, additional, Ren, Xiubao, additional, Aggarwal, Charu, additional, Mangrolia, Drishty, additional, Cohen, Roger, additional, Weinstein, Gregory, additional, Morrow, Matthew, additional, Bauml, Joshua, additional, Kraynyak, Kim, additional, Boyer, Jean, additional, Yan, Jian, additional, Lee, Jessica, additional, Humeau, Laurent, additional, Oyola, Sandra, additional, Duff, Susan, additional, Weiner, David, additional, Yang, Zane, additional, Bagarazzi, Mark, additional, McNeel, Douglas G., additional, Eickhoff, Jens, additional, Jeraj, Robert, additional, Staab, Mary Jane, additional, Straus, Jane, additional, Rekoske, Brian, additional, Liu, Glenn, additional, Melssen, Marit, additional, Grosh, William, additional, Varhegyi, Nikole, additional, Galeassi, Nadejda, additional, Deacon, Donna H., additional, Gaughan, Elizabeth, additional, Ghisoli, Maurizio, additional, Barve, Minal, additional, Mennel, Robert, additional, Wallraven, Gladice, additional, Manning, Luisa, additional, Senzer, Neil, additional, Nemunaitis, John, additional, Ogasawara, Masahiro, additional, Ota, Shuichi, additional, Peace, Kaitlin M., additional, Hale, Diane F., additional, Vreeland, Timothy J., additional, Jackson, Doreen O., additional, Berry, John S., additional, Trappey, Alfred F., additional, Herbert, Garth S., additional, Clifton, Guy T., additional, Hardin, Mark O., additional, Toms, Anne, additional, Qiao, Na, additional, Litton, Jennifer, additional, Peoples, George E., additional, Mittendorf, Elizabeth A., additional, Ghamsari, Lila, additional, Flano, Emilio, additional, Jacques, Judy, additional, Liu, Biao, additional, Havel, Jonathan, additional, Makarov, Vladimir, additional, Chan, Timothy A., additional, Flechtner, Jessica B., additional, Facciponte, John, additional, Ugel, Stefano, additional, De Sanctis, Francesco, additional, Coukos, George, additional, Paris, Sébastien, additional, Pottier, Agnes, additional, Levy, Laurent, additional, Lu, Bo, additional, Cappuccini, Federica, additional, Pollock, Emily, additional, Bryant, Richard, additional, Hamdy, Freddie, additional, Hill, Adrian, additional, Redchenko, Irina, additional, Sultan, Hussein, additional, Kumai, Takumi, additional, Fesenkova, Valentyna, additional, Celis, Esteban, additional, Fernando, Ingrid, additional, Palena, Claudia, additional, David, Justin M., additional, Gabitzsch, Elizabeth, additional, Jones, Frank, additional, Gulley, James L., additional, Herranz, Mireia Uribe, additional, Wada, Hiroshi, additional, Shimizu, Atsushi, additional, Osada, Toshihiro, additional, Fukaya, Satoshi, additional, Sasaki, Eiji, additional, Abolhalaj, Milad, additional, Askmyr, David, additional, Lundberg, Kristina, additional, Albrekt, Ann-Sofie, additional, Greiff, Lennart, additional, Lindstedt, Malin, additional, Flies, Dallas B., additional, Higuchi, Tomoe, additional, Ornatowski, Wojciech, additional, Harris, Jaryse, additional, Adams, Sarah F., additional, Aguilera, Todd, additional, Rafat, Marjan, additional, Castellini, Laura, additional, Shehade, Hussein, additional, Kariolis, Mihalis, additional, Jang, Dadi, additional, vonEbyen, Rie, additional, Graves, Edward, additional, Ellies, Lesley, additional, Rankin, Erinn, additional, Koong, Albert, additional, Giaccia, Amato, additional, Ajina, Reham, additional, Wang, Shangzi, additional, Smith, Jill, additional, Pierobon, Mariaelena, additional, Jablonski, Sandra, additional, Petricoin, Emanuel, additional, Weiner, Louis M., additional, Sherry, Lorcan, additional, Waller, John, additional, Anderson, Mark, additional, Bigley, Alison, additional, Bernatchez, Chantale, additional, Haymaker, Cara, additional, Kluger, Harriet, additional, Tetzlaff, Michael, additional, Jackson, Natalie, additional, Gergel, Ivan, additional, Tagliaferri, Mary, additional, Hwu, Patrick, additional, Snzol, Mario, additional, Hurwitz, Michael, additional, Barberi, Theresa, additional, Martin, Allison, additional, Suresh, Rahul, additional, Barakat, David, additional, Harris-Bookman, Sarah, additional, Drake, Charles, additional, Friedman, Alan, additional, Berkey, Sara, additional, Downs-Canner, Stephanie, additional, Edwards, Robert P., additional, Curiel, Tyler, additional, Odunsi, Kunle, additional, Bruno, Tullia C., additional, Moore, Brandon, additional, Squalls, Olivia, additional, Ebner, Peggy, additional, Waugh, Katherine, additional, Mitchell, John, additional, Franklin, Wilbur, additional, Merrick, Daniel, additional, McCarter, Martin, additional, Palmer, Brent, additional, Kern, Jeffrey, additional, Vignali, Dario, additional, Slansky, Jill, additional, Chan, Anissa S. H., additional, Qiu, Xiaohong, additional, Fraser, Kathryn, additional, Jonas, Adria, additional, Ottoson, Nadine, additional, Gordon, Keith, additional, Kangas, Takashi O., additional, Leonardo, Steven, additional, Ertelt, Kathleen, additional, Walsh, Richard, additional, Uhlik, Mark, additional, Graff, Jeremy, additional, Bose, Nandita, additional, Gupta, Ravi, additional, Mandloi, Nitin, additional, Paul, Kiran, additional, Patil, Ashwini, additional, Sathian, Rekha, additional, Mohan, Aparna, additional, Manoharan, Malini, additional, Chaudhuri, Amitabha, additional, Chen, Yu, additional, Lin, Jing, additional, Ye, Yun-bin, additional, Xu, Chun-wei, additional, Chen, Gang, additional, Guo, Zeng-qing, additional, Komarov, Andrey, additional, Chenchik, Alex, additional, Makhanov, Michael, additional, Frangou, Costa, additional, Zheng, Yi, additional, Coltharp, Carla, additional, Unfricht, Darryn, additional, Dilworth, Ryan, additional, Fridman, Leticia, additional, Liu, Linying, additional, Rajopadhye, Milind, additional, Miller, Peter, additional, Concha-Benavente, Fernando, additional, Bauman, Julie, additional, Trivedi, Sumita, additional, Srivastava, Raghvendra, additional, Ohr, James, additional, Heron, Dwight, additional, Duvvuri, Uma, additional, Kim, Seungwon, additional, Torrey, Heather, additional, Mera, Toshi, additional, Okubo, Yoshiaki, additional, Vanamee, Eva, additional, Foster, Rosemary, additional, Faustman, Denise, additional, Stack, Edward, additional, Izaki, Daisuke, additional, Beck, Kristen, additional, Jia, Dan Tong, additional, Armenta, Paul, additional, White-Stern, Ashley, additional, Marks, Douglas, additional, Taback, Bret, additional, Horst, Basil, additional, Glickman, Laura Hix, additional, Kanne, David B., additional, Gauthier, Kelsey S., additional, Desbien, Anthony L., additional, Francica, Brian, additional, Leong, Justin L., additional, Sung, Leonard, additional, Metchette, Ken, additional, Kasibhatla, Shailaja, additional, Pferdekamper, Anne Marie, additional, Zheng, Lianxing, additional, Cho, Charles, additional, Feng, Yan, additional, McKenna, Jeffery M., additional, Tallarico, John, additional, Bender, Steven, additional, Ndubaku, Chudi, additional, McWhirter, Sarah M., additional, Gugel, Elena Gonzalez, additional, Bell, Charles J. M., additional, Munk, Adiel, additional, Muniz, Luciana, additional, Bhardwaj, Nina, additional, Zhao, Fei, additional, Evans, Kathy, additional, Xiao, Christine, additional, Holtzhausen, Alisha, additional, Hanks, Brent A., additional, Scholler, Nathalie, additional, Yin, Catherine, additional, Van der Meijs, Pien, additional, Prantner, Andrew M., additional, Krejsa, Cecile M., additional, Smith, Leia, additional, Johnson, Brian, additional, Branstetter, Daniel, additional, Stein, Paul L., additional, Jaen, Juan C., additional, Tan, Joanne BL, additional, Chen, Ada, additional, Park, Timothy, additional, Powers, Jay P., additional, Sexton, Holly, additional, Xu, Guifen, additional, Young, Steve W., additional, Schindler, Ulrike, additional, Deng, Wentao, additional, Klinke, David John, additional, Komar, Hannah M., additional, Serpa, Gregory, additional, Elnaggar, Omar, additional, Hart, Philip, additional, Schmidt, Carl, additional, Dillhoff, Mary, additional, Jin, Ming, additional, Ostrowski, Michael C., additional, Koti, Madhuri, additional, Au, Katrina, additional, Peterson, Nichole, additional, Truesdell, Peter, additional, Reid-Schachter, Gillian, additional, Graham, Charles, additional, Craig, Andrew, additional, Francis, Julie-Ann, additional, Kotlan, Beatrix, additional, Balatoni, Timea, additional, Farkas, Emil, additional, Toth, Laszlo, additional, Ujhelyi, Mihaly, additional, Savolt, Akos, additional, Doleschall, Zoltan, additional, Horvath, Szabolcs, additional, Eles, Klara, additional, Olasz, Judit, additional, Csuka, Orsolya, additional, Kasler, Miklos, additional, Liszkay, Gabriella, additional, Barnea, Eytan, additional, Blakely, Collin, additional, Flynn, Patrick, additional, Goodman, Reid, additional, Bueno, Raphael, additional, Sugarbaker, David, additional, Jablons, David, additional, Broaddus, V. Courtney, additional, West, Brian, additional, Kunk, Paul R., additional, Obeid, Joseph M., additional, Winters, Kevin, additional, Pramoonjago, Patcharin, additional, Stelow, Edward B., additional, Bauer, Todd W., additional, Rahma, Osama E., additional, Lamble, Adam, additional, Kosaka, Yoko, additional, Huang, Fei, additional, Saser, Kate A., additional, Adams, Homer, additional, Tognon, Christina E., additional, Laderas, Ted, additional, McWeeney, Shannon, additional, Loriaux, Marc, additional, Tyner, Jeffery W., additional, Druker, Brian J., additional, Lind, Evan F., additional, Liu, Zhuqing, additional, Lu, Shanhong, additional, Kane, Lawrence P., additional, Shayan, Gulidanna, additional, Femel, Julia, additional, Lane, Ryan, additional, Booth, Jamie, additional, Lund, Amanda W., additional, Rodriguez, Anthony, additional, Engelhard, Victor H., additional, Metelli, Alessandra, additional, Wu, Bill X., additional, Fugle, Caroline W., additional, Saleh, Rachidi, additional, Sun, Shaoli, additional, Wu, Jennifer, additional, Liu, Bei, additional, Li, Zihai, additional, Morris, Zachary S., additional, Guy, Emily I., additional, Heinze, Clinton, additional, Kler, Jasdeep, additional, Gressett, Monica M., additional, Werner, Lauryn R., additional, Gillies, Stephen D., additional, Korman, Alan J., additional, Loibner, Hans, additional, Hank, Jacquelyn A., additional, Rakhmilevich, Alexander L., additional, Harari, Paul M., additional, Sondel, Paul M., additional, Huelsmann, Erica, additional, Broucek, Joseph, additional, Brech, Dorothee, additional, Straub, Tobias, additional, Irmler, Martin, additional, Beckers, Johannes, additional, Buettner, Florian, additional, Schaeffeler, Elke, additional, Schwab, Matthias, additional, Noessner, Elfriede, additional, Wolfreys, Alison, additional, Da Costa, Andre, additional, Silva, John, additional, Crosby, Andrea, additional, Staelens, Ludovicus, additional, Craggs, Graham, additional, Cauvin, Annick, additional, Mason, Sean, additional, Paterson, Alison M., additional, Lake, Andrew C., additional, Armet, Caroline M., additional, O’Connor, Rachel W., additional, Hill, Jonathan A., additional, Normant, Emmanuel, additional, Adam, Ammar, additional, Biniszkiewicz, Detlev M., additional, Chappel, Scott C., additional, Palombella, Vito J., additional, Holland, Pamela M., additional, Becker, Annette, additional, Leleti, Manmohan R., additional, Newcomb, Eric, additional, Tan, Joanne B. L., additional, Rapisuwon, Suthee, additional, Radfar, Arash, additional, Gardner, Kellie, additional, Gibney, Geoffrey, additional, Atkins, Michael, additional, Rennier, Keith R., additional, Crowder, Robert, additional, Wang, Ping, additional, Pachynski, Russell K., additional, Carrero, Rosa M. Santana, additional, Rivas, Sarai, additional, Beceren-Braun, Figen, additional, Anthony, Scott, additional, Schluns, Kimberly S., additional, Sawant, Deepali, additional, Chikina, Maria, additional, Yano, Hiroshi, additional, Workman, Creg, additional, Salerno, Elise, additional, Mauldin, Ileana, additional, Deacon, Donna, additional, Shea, Sofia, additional, Pinczewski, Joel, additional, Gajewski, Thomas, additional, Spranger, Stefani, additional, Horton, Brendan, additional, Suzuki, Akiko, additional, Leland, Pamela, additional, Joshi, Bharat H., additional, Puri, Raj K., additional, Sweis, Randy F., additional, Bao, Riyue, additional, Luke, Jason, additional, Theodoraki, Marie-Nicole, additional, Mogundo, Frances-Mary, additional, Won, Haejung, additional, Moreira, Dayson, additional, Gao, Chan, additional, Zhao, Xingli, additional, Duttagupta, Priyanka, additional, Jones, Jeremy, additional, D’Apuzzo, Massimo, additional, and Pal, Sumanta, additional

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43. Abstract A034: Boosting the efficacy of PD-L1 blockade with oncolytic vaccine for improved antitumor responses in melanoma

Author

Capasso, Cristian, primary, Tähtinen, Siri, additional, Frascaro, Federica, additional, Carpi, Sara, additional, Fusciello, Manlio, additional, Cardella, Davide, additional, Cropp, Daniela, additional, Peltonen, Karita, additional, Martins, Beatriz, additional, Sjöberg, Madeleine, additional, Pesonen, Sari, additional, Ranki, Tuuli, additional, Kuryk, Lukasz, additional, Ylösmäki, Erkko, additional, and Cerullo, Vincenzo, additional

Published
2016
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45. Rational engineering of microRNA-regulated viruses for cancer gene therapy

Author

Ylösmäki, Erkko, University of Helsinki, Faculty of Medicine, Haartman Institute, Department of virology, Helsingin yliopisto, lääketieteellinen tiedekunta, kliinisteoreettinen laitos, Helsingfors universitet, medicinska fakulteten, Haartman institutet, Essand, Magnus, and Saksela, Kalle

Subjects
viruses, lääketiede
Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that have important regulatory roles in a wide range of biological processes. miRNAs are often expressed in a tissue- and/or differentiation state-specific patterns, and it is estimated that miRNAs can regulate the expression of more than 50% of all human genes. We have exploited these tissue-specific miRNA expression patterns in the modification of viral replicative tropism. In order to engineer the replicative tropism of oncolytic adenoviruses, we developed a recombinant adenovirus that in the 3 UTR of the critical E1A gene contains sequences complementary to the liver-specific miRNA miR122. This allowed us to generate a novel recombinant adenovirus that was severely attenuated in human liver, but replicated to high titres in colorectal cancer. Systemic injection of miR122-targeted adenovirus into mice did not induce liver toxicity. In a human lung cancer xenograft mouse model this miR122-targeted adenovirus showed potent antitumour activity. We also studied the possibility to exploit neuron-specific miRNA expression patterns in the modification of tissue tropism of an alphavirus Semliki Forest virus (SFV). We engineered SFV genome to contain sequences complementary to the neuron-specific miRNA miR124. In vitro characterization of this novel virus showed that the modification of the SFV genome per se did not affect polyprotein processing or oncolytic potency. Intraperitoneally administered miR124-targeted SFV displayed an attenuated spread into the central nervous system (CNS) and increased survival of infected mice. Also, mice pre-infected with miR124-targeted SFV elicited strong protective immunity against otherwise lethal challenge with a highly virulent wild-type SFV strain. In conclusion, these results show that miRNA-targeting is a potent new strategy to engineer viral tropism in development of safer and more efficient reagents for virotherapy applications. MikroRNA:t (miRNA) ovat pieniä ei-koodaavia RNA molekyylejä joilla on tärkeä tehtävä useiden erilaisten biologisten prosessien säätelyssä. MiRNA:t ekpressoituvat usein kudos- ja/tai kehitysvaihespesifisesti sekä säätelevät jopa yli 50 prosenttia kaikista ihmisen geeneistä. Tässä väitöskirjatutkimuksessa pyrimme käyttämään hyväksi miRNA:iden kudosspesifistä ekpressiota virusten kudostropismin muokkaamisessa vähentääksemme virusvektoreiden haitallista kudostoksisuutta. Muokataksemme adenovirusvektoreiden kudostropismia, kehitimme uudentyyppisen adenoviruksen jonka E1A-geenin 3 ei-koodaavalle alueelle lisäsimme ihmisen maksaspesifisen miRNA miR122:n tunnistussekvenssejä. Tunnistussekvenssien lisäyksellä saimme aikaan adenoviruksen (miR122-targetoitu adenovirus) jonka replikaatiokyky oli huomattavasti heikentynyt ihmisen maksassa, mutta pystyi replikoitumaan voimakkaasti perä- ja paksusuolisyöpäkudoksessa. Hiireen systeemisesti injisoitu miR122-targetoitu adenovirus ei aiheuttanut maksatoksisuutta. Ihmisen keuhkosyöpähiirimallissa miR122-targetoitu virus tappoi tehokkaasti syöpäsoluja. Tässä väitöskirjatutkimuksessa tutkimme myös hermosoluspesifisen miRNA miR124:n hyväksikäyttöä Semliki Forest-viruksen (SFV) kudostropismin muokkauksessa. Kehitimme SFV:n jonka genomiin oli sisällytetty miR124:n tunnistussekvenssejä. In vitro-kokeilla osoitimme tämän miR124-targetoidun SFV:n proteiinien prosessoituvan normaalisti sekä onkolyyttisen tehon säilyneen villityypin viruksen kaltaisena. Vatsaonteloon injisoitu miR124-targetoitu SFV levisi hyvin heikosti keskushermostossa joka johti vähentyneeseen neurotoksisuuteen. Osoitimme myös miR124-targetoidun viruksen toimivan tehokkaana rokotteena erittäin patogeeniselle L10 SFV-kannalle. Tässä väitöskirjatutkimuksessa pystyimme osoittamaan miRNA-targetoinnin olevan tehokas uusi tapa muokata virusten kudostropismia ja parantaa virusvektoreiden turvallisuutta.

Published
2013

46. MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma

Author

Martikainen, Miika, primary, Niittykoski, Minna, additional, von und zu Fraunberg, Mikael, additional, Immonen, Arto, additional, Koponen, Susanna, additional, van Geenen, Maartje, additional, Vähä-Koskela, Markus, additional, Ylösmäki, Erkko, additional, Jääskeläinen, Juha E., additional, Saksela, Kalle, additional, and Hinkkanen, Ari, additional

Published
2015
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48. Melanocarpus albomyces –lakkaasin C-terminuksen mutagenisointi:Pro gradu

Author

Ylösmäki, Erkko

Abstract

Tutkielman kirjallisessa osassa tarkastellaan ensin tunnetuimpia sini-kuparioksidaaseja yleisellä tasolla, jonka jälkeen tarkastellaan lakkaaseja, niiden evoluutiota, toimintaa ja levinneisyyttä hieman lähemmin. Tämän jälkeen keskitytään sienten lakkaasien ominaisuuksien, geenisekvenssien, kiderakenteiden seka toimintamekanismin tarkasteluun. Melanocarpus albomyces -lakkaasin ominaisuuksia, lakkaasigeeniä, ja sen kloonausta seka M. albomyces -lakkaasin rakennetta tarkastellaan yksityiskohtaisesti. Lopuksi käydään läpi lakkaasien heterologiseen tuottoon sekä lakkaasien mahdollisiin teollisiin sovelluksiin liittyvää kirjallisuutta. Tutkielman kokeellinen osa suoritettiin VTT Biotekniikan Homeiden molekyylibiologia- ja Entsyymitekniikka-tutkimusryhmissä Markku Saloheimon ja Kristiina Kruusin ohjauksessa. Kokeellisessa osassa kerrotaan ensin kahden ekspressiokonstruktin tuotosta Trichoderma reeseissä sekä konstruktien analysoinnista immunoblottauksen avulla. Toisessa konstruktissa oli pelkkä M. albomyces -lakkaasin (MaL) cDNA, ja toisessa MaL:n cDNA fuusioituna hfpl-geenin kanssa. Tutkimuksessa havaittiin, että HFB1-lakkaasi-fuusioproteiini pilkkoutuu jo solun sisällä, eikä intaktia fuusioproteiinia näyttänyt erittyvän kasvuliuokseen. Tutkimuksen toisessa osassa kerrotaan neljän erilaisen C-terminaalisen lakkaasimutantin DNA-konstruktien valmistuksesta, niiden transformoinnista Trichoderma reeseihin, mutanttiproteiinien tuotosta, puhdistuksesta sekä aktiivisuusmäärityksistä. Tutkimuksessa kävi ilmi, että kolmella lakkaasimutantilla (M1, M2 ja M4) oli selvä vaikutus proteiinin tuottoon T. reeseissä. M1- ja M2-lakkaasimutantit olivat myös osittain hajonneina kasvuliuoksessa, joka viittaisi siihen, etta lakkaasimutantit ovat villityypin lakkaasia herkempiä T. reesein tuottamille proteaaseille. Lisäksi kävi ilmi, että M1-, M2- ja M4-lakkaasimutanttien katalyyttinen aktiivisuus oli selvästi villityypin lakkaasia matalampaa. M3-mutaatiolla ei ollut selvää vaikutusta lakkaasin tuottoon eikä sen katalyyttiseen aktiivisuuteen. M3-mutaatio näytti kuitenkin muuttavan lakkaasin prosessointia, sillä C-terminaalisen sekvensoinnin tuloksista voitiin päätellä, että SDS-PAGE geelillä puhtaalta näyttänyt näyte sisälsi monia eri kohdista pilkottuja proteiinipopulaatioita.

Published
2005

49. MicroRNA-Mediated Suppression of Oncolytic Adenovirus Replication in Human Liver

Author

University of Helsinki, Haartman Institute, University of Helsinki, Research Programs Unit, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, IV kirurgian klinikka, Ylösmäki, Erkko, Lavilla Alonso, Sergio, Jäämaa, Sari Susanna, Vaha-Koskela, Markus, af Hällström, Taija Maria, Hemminki, Akseli, Arola, Johanna, Mäkisalo, Heikki, Saksela, Kalle, University of Helsinki, Haartman Institute, University of Helsinki, Research Programs Unit, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, IV kirurgian klinikka, Ylösmäki, Erkko, Lavilla Alonso, Sergio, Jäämaa, Sari Susanna, Vaha-Koskela, Markus, af Hällström, Taija Maria, Hemminki, Akseli, Arola, Johanna, Mäkisalo, Heikki, and Saksela, Kalle

Published
2013

50. Rational engineering of microRNA-regulated viruses for cancer gene therapy

Author

Helsingin yliopisto, lääketieteellinen tiedekunta, kliinisteoreettinen laitos, Helsingfors universitet, medicinska fakulteten, Haartman institutet, University of Helsinki, Faculty of Medicine, Haartman Institute, Department of virology, Ylösmäki, Erkko, Helsingin yliopisto, lääketieteellinen tiedekunta, kliinisteoreettinen laitos, Helsingfors universitet, medicinska fakulteten, Haartman institutet, University of Helsinki, Faculty of Medicine, Haartman Institute, Department of virology, and Ylösmäki, Erkko

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that have important regulatory roles in a wide range of biological processes. miRNAs are often expressed in a tissue- and/or differentiation state-specific patterns, and it is estimated that miRNAs can regulate the expression of more than 50% of all human genes. We have exploited these tissue-specific miRNA expression patterns in the modification of viral replicative tropism. In order to engineer the replicative tropism of oncolytic adenoviruses, we developed a recombinant adenovirus that in the 3 UTR of the critical E1A gene contains sequences complementary to the liver-specific miRNA miR122. This allowed us to generate a novel recombinant adenovirus that was severely attenuated in human liver, but replicated to high titres in colorectal cancer. Systemic injection of miR122-targeted adenovirus into mice did not induce liver toxicity. In a human lung cancer xenograft mouse model this miR122-targeted adenovirus showed potent antitumour activity. We also studied the possibility to exploit neuron-specific miRNA expression patterns in the modification of tissue tropism of an alphavirus Semliki Forest virus (SFV). We engineered SFV genome to contain sequences complementary to the neuron-specific miRNA miR124. In vitro characterization of this novel virus showed that the modification of the SFV genome per se did not affect polyprotein processing or oncolytic potency. Intraperitoneally administered miR124-targeted SFV displayed an attenuated spread into the central nervous system (CNS) and increased survival of infected mice. Also, mice pre-infected with miR124-targeted SFV elicited strong protective immunity against otherwise lethal challenge with a highly virulent wild-type SFV strain. In conclusion, these results show that miRNA-targeting is a potent new strategy to engineer viral tropism in development of safer and more efficient reagents for virotherapy applications., MikroRNA:t (miRNA) ovat pieniä ei-koodaavia RNA molekyylejä joilla on tärkeä tehtävä useiden erilaisten biologisten prosessien säätelyssä. MiRNA:t ekpressoituvat usein kudos- ja/tai kehitysvaihespesifisesti sekä säätelevät jopa yli 50 prosenttia kaikista ihmisen geeneistä. Tässä väitöskirjatutkimuksessa pyrimme käyttämään hyväksi miRNA:iden kudosspesifistä ekpressiota virusten kudostropismin muokkaamisessa vähentääksemme virusvektoreiden haitallista kudostoksisuutta. Muokataksemme adenovirusvektoreiden kudostropismia, kehitimme uudentyyppisen adenoviruksen jonka E1A-geenin 3 ei-koodaavalle alueelle lisäsimme ihmisen maksaspesifisen miRNA miR122:n tunnistussekvenssejä. Tunnistussekvenssien lisäyksellä saimme aikaan adenoviruksen (miR122-targetoitu adenovirus) jonka replikaatiokyky oli huomattavasti heikentynyt ihmisen maksassa, mutta pystyi replikoitumaan voimakkaasti perä- ja paksusuolisyöpäkudoksessa. Hiireen systeemisesti injisoitu miR122-targetoitu adenovirus ei aiheuttanut maksatoksisuutta. Ihmisen keuhkosyöpähiirimallissa miR122-targetoitu virus tappoi tehokkaasti syöpäsoluja. Tässä väitöskirjatutkimuksessa tutkimme myös hermosoluspesifisen miRNA miR124:n hyväksikäyttöä Semliki Forest-viruksen (SFV) kudostropismin muokkauksessa. Kehitimme SFV:n jonka genomiin oli sisällytetty miR124:n tunnistussekvenssejä. In vitro-kokeilla osoitimme tämän miR124-targetoidun SFV:n proteiinien prosessoituvan normaalisti sekä onkolyyttisen tehon säilyneen villityypin viruksen kaltaisena. Vatsaonteloon injisoitu miR124-targetoitu SFV levisi hyvin heikosti keskushermostossa joka johti vähentyneeseen neurotoksisuuteen. Osoitimme myös miR124-targetoidun viruksen toimivan tehokkaana rokotteena erittäin patogeeniselle L10 SFV-kannalle. Tässä väitöskirjatutkimuksessa pystyimme osoittamaan miRNA-targetoinnin olevan tehokas uusi tapa muokata virusten kudostropismia ja parantaa virusvektoreiden turvallisuutta.

Published
2013

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