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3. Monocytes in leukapheresis products affect the outcome of CD19-targeted CAR T-cell therapy in lymphoma patients

Author

Carniti, Cristiana, primary, Caldarelli, Nicole Maria, additional, Agnelli, Luca, additional, Torelli, Tommaso, additional, Ljevar, Silva, additional, Jonnalagadda, Sadhana, additional, Zanirato, Giada, additional, Fardella, Eugenio, additional, Stella, Federico, additional, Lorenzini, Daniele, additional, Brich, Silvia, additional, Arienti, Flavio, additional, Dodero, Anna, additional, Chiappella, Annalisa, additional, Magni, Martina, additional, and Corradini, Paolo, additional

Published
2024
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5. Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment

Author

Tazzari, Marcella, Indio, Valentina, Vergani, Barbara, De Cecco, Loris, Rini, Francesca, Negri, Tiziana, Camisaschi, Chiara, Fiore, Marco, Stacchiotti, Silvia, Dagrada, G. Paolo, Casali, Paolo G., Gronchi, Alessandro, Astolfi, Annalisa, Pantaleo, Maria A., Villa, Antonello, Lombardo, Claudia, Arienti, Flavio, Pilotti, Silvana, Rivoltini, Licia, and Castelli, Chiara

Published
2017
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6. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma

Author

Huber, Veronica, Vallacchi, Viviana, Fleming, Viktor, Hu, Xiaoying, Cova, Agata, Dugo, Matteo, Shahaj, Eriomina, Sulsenti, Roberta, Vergani, Elisabetta, Filipazzi, Paola, De Laurentiis, Angela, Lalli, Luca, Di Guardo, Lorenza, Patuzzo, Roberto, Vergani, Barbara, Casiraghi, Elena, Cossa, Mara, Gualeni, Ambra, Bollati, Valentina, Arienti, Flavio, De Braud, Filippo, Mariani, Luigi, Villa, Antonello, Altevogt, Peter, Umansky, Viktor, Rodolfo, Monica, and Rivoltini, Licia

Subjects
Cancer patients -- Care and treatment, Immunotherapy -- Usage, MicroRNA -- Research, Suppressor cells -- Research, Treatment outcome -- Analysis, Cancer treatment, Tumors, Cell death, Infection, Melanoma, Health care industry
Abstract

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs ([CD14.sup.+][HLA-DR.sup.neg] cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs were increased in circulating [CD14.sup.+] monocytes, plasma, and tumor samples, where they correlated with the myeloid cell infiltrate. In plasma, their baseline levels clustered with the clinical efficacy of CTLA-4 or programmed cell death protein 1 (PD-1) blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome., IntroductionImmunotherapy with immune checkpoint inhibitors (ICIs) has achieved a remarkable improvement in overall survival (OS) in different tumor histologies, albeit the majority of patients display intrinsic resistance (1). The response [...]

Published
2018
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8. Supplementary Data from Induction of Both CD8+ and CD4+ T-Cell–Mediated Responses in Colorectal Cancer Patients by Colon Antigen-1

Author

Maccalli, Cristina, primary, Di Cristanziano, Veronica, primary, Fodale, Valentina, primary, Corsi, Domenico, primary, D'Agostino, Giuseppina, primary, Petrangeli, Valentina, primary, Laurenti, Luca, primary, Guida, Sofia, primary, Mazzocchi, Arabella, primary, Arienti, Flavio, primary, Perrone, Maria P., primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, Zagonel, Vittorina, primary, Tartaglia, Marco, primary, Parmiani, Giorgio, primary, and Belardelli, Filippo, primary

Published
2023
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9. Data from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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10. Supplementary Figure 1 from Immunization of Stage IV Melanoma Patients with Melan-A/MART-1 and gp100 Peptides plus IFN-α Results in the Activation of Specific CD8+ T Cells and Monocyte/Dendritic Cell Precursors

Author

Di Pucchio, Tiziana, primary, Pilla, Lorenzo, primary, Capone, Imerio, primary, Ferrantini, Maria, primary, Montefiore, Enrica, primary, Urbani, Francesca, primary, Patuzzo, Roberto, primary, Pennacchioli, Elisabetta, primary, Santinami, Mario, primary, Cova, Agata, primary, Sovena, Gloria, primary, Arienti, Flavio, primary, Lombardo, Claudia, primary, Lombardi, Arianna, primary, Caporaso, Patrizia, primary, D'Atri, Stefania, primary, Marchetti, Paolo, primary, Bonmassar, Enzo, primary, Parmiani, Giorgio, primary, Belardelli, Filippo, primary, and Rivoltini, Licia, primary

Published
2023
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11. Supplementary Table 1 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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12. Supplementary Figure 1 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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13. Supplementary Table 5 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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14. Supplementary Table 4 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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15. Supplementary Figure 2 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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19. Supplementary Figure 3 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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21. Supplementary Methods from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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22. Supplementary Table 3 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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23. Supplementary Figures 1-10 from Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma

Author

Anichini, Andrea, primary, Molla, Alessandra, primary, Vegetti, Claudia, primary, Bersani, Ilaria, primary, Zappasodi, Roberta, primary, Arienti, Flavio, primary, Ravagnani, Fernando, primary, Maurichi, Andrea, primary, Patuzzo, Roberto, primary, Santinami, Mario, primary, Pircher, Hanspeter, primary, Di Nicola, Massimo, primary, and Mortarini, Roberta, primary

Published
2023
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24. Supplementary Table 2 from Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Author

Vallacchi, Viviana, primary, Vergani, Elisabetta, primary, Camisaschi, Chiara, primary, Deho, Paola, primary, Cabras, Antonello D., primary, Sensi, Marialuisa, primary, De Cecco, Loris, primary, Bassani, Niccolò, primary, Ambrogi, Federico, primary, Carbone, Antonino, primary, Crippa, Federica, primary, Vergani, Barbara, primary, Frati, Paola, primary, Arienti, Flavio, primary, Patuzzo, Roberto, primary, Villa, Antonello, primary, Biganzoli, Elia, primary, Canevari, Silvana, primary, Santinami, Mario, primary, Castelli, Chiara, primary, Rivoltini, Licia, primary, and Rodolfo, Monica, primary

Published
2023
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28. Predictors of CD34+ Cell Mobilization and Collection in Adult Men With Germ Cell Tumors: Implications for the Salvage Treatment Strategy

Author

Necchi, Andrea, Miceli, Rosalba, Pedrazzoli, Paolo, Giannatempo, Patrizia, Secondino, Simona, Di Nicola, Massimo, Farè, Elena, Raggi, Daniele, Magni, Michele, Matteucci, Paola, Longoni, Paolo, Milanesi, Marco, Paternò, Emanuela, Ravagnani, Fernando, Arienti, Flavio, Nicolai, Nicola, Salvioni, Roberto, Carlo-Stella, Carmelo, and Gianni, Alessandro M.

Published
2014
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29. Antiepileptic drug discontinuation by people with epilepsy in the general population

Author

Giussani, Giorgia, Bianchi, Elisa, Canelli, Valentina, Erba, Giuseppe, Franchi, Carlotta, Nobili, Alessandro, Sander, Josemir W., Beghi, Ettore, Agostoni, Elio, Airoldi, Larissa, Basso, Francesco, Carpanelli, Marialuisa, Di Stefano, Mariolina, Magnoni, Andrea, Martinelli, Ottaviano, Rigamonti, Andrea, Salmaggi, Andrea, Stanzani, Lorenzo, Volpe, Cristina, Zanotta, Nicoletta, Zucca, Claudio, Agudio, Marco, Arienti, Flavio, Arrigoni, Graziano Rocco, Balestra, Giancarlo, Ballabio, Piercarla, Balossi, Stefano Marco, Baratti, Maria Rita, Barteselli, Fabrizia Enrica, Bellani, Fausto, Bellani, Mauro, Bellini, Gianpiero, Beretta, Pier Aldo, Beretta, Roberto, Bergamini, Massimo, Bertella, Annalisa, Bertolini, Francesco, Bevilacqua, Rolando, Bianchi, Marcellino Arturo, Bigiolli, Patrizia, Binda, Giuseppe, Biondelli, Gigliola, Bodega, Libero, Bolis, Edoardo Giovanni, Vincenzo, Marco, Bolla, Carlo, Bonacina, Carlo Ambrogio, Bonfanti, Marco, Borghetti, Fausta, Brambilla, Roberto, Brancaleone, Wilma, Brusadelli, Francesco, Bub, Sabine, Caccia, Giovanna, Caglio, Myriam, Rossi, Carlo Calvi, Capra, Daniela, Carone, Davide, Carì, Giuseppe, Carrera, Silvio, Cavenago, Rosalia, Cecchetti, Maria Luisa, Centonze, Bice Antonella, Cereghini, Fabio, Cerrone, Ciro, Ciappetta, Maria Pia, Cogliati, Bruno, Colombano, Ombretta, Colombo, Alberto, Colombo, Daniela, Corti, Maria Lia, Cremonini, Nicla, Crippa, Marco, Crippa, Rolando Antonio, Crotta, Mario, Curto, Salvatore, Daielli, Patrizia, De Gilio, Domenico, De Pascalis, Giuseppe Pasquale, Decet, Elena, Della Morte, Luigi, Duvia, Felice, Favorito, Antonia, Ferrario, Roberto, Fezzi, Luigi, Laura Finzi, Angela, Fiorentino, Bruno Ugo, Fornaciari, Agnese, Franceschetti, Silvana, Fulconis, Fabio, Fumagalli, Giovanni, Fumagalli, Maurizio, Galbiati, Giuseppe, Andrea Galimberti, Carlo, Gecchele, Donatella, Ghiazza, Barbara, Ghislanzoni, Paolo, Gioffredi, Laura, Hassibi, Taraneh, Julita, Simone, Leone, Giuseppe, Levi, Claudio, Locatelli, Giovanni, Locati, AnnaAlessandra, Longhi, Enrico Giovanni, Lukacova, Ingrid, Manfroi, Mauro Giovanni, Manzoni, Paola, Marcolini, Claudio, Minicucci, Fabio, Martini, Mohammed Safwan, Masperi, Rita, Mayan, Sussele, Mazzoleni, Valeria, Menga, Antonio, Merlini, Fiorella, Messina, Enrico, Micheli, Marta, Micò, Rocco, Millul, Andrea, Montini, Barbara, Palazzuolo, Alberto, Panzeri, Silvano Primo, Passoni, Giovanni, Pensotti, Laura, Petrone, Maria Marcella, Pezzuto, Roberto, Pigazzini, Elisabetta, Pirovano, Nicoletta, Pontiggia, Margherita, Pozzi, Roberto, Quadrelli, Carlo, Rampello, Filomena, Realini, Marco, Righetti, Giovanni, Ripa, Cesare, Rivetta, Sonia, Romeo, Antonino, Rota, Carlo, Rusconi, Tiziana, Santarpia, Andrea, Santi, Ivana, Sciani, Luigi, Scoccimarro, Gianni, Scopinaro, Eugenio, Semerano, Angelo Giuseppe, Sferco, Daniela, Sirtori, Anna Ersilia, Spandri, Angela, Spinelli, Bruno, Stefanoni, Fausto, Taiana, Raffaele, Tamagnini, Libero, Tassi, Laura, Tentori, Giorgio, Teodoro, Augusto, Tinterova, Katerina, Tocchetti, Ampelio, Todeschini, Michela, Trezza, Lorenzo, Valsecchi, Valter, Vanini, Roberto, Vercelloni, Claudio Felice, Villella, Anna, Viola, Maria, Vismara, Pietro, and Zoboli, Daniele Mario

Published
2017
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30. A Microsatellite in the Coding Sequence of HLA-A/B Is a Mutation Hotspot in Colon Cancer With Microsatellite Instability

Author

Raab, William J., primary, Mazzocchi, Arabella, additional, Radice, Paolo, additional, Sahoo, Debashis, additional, Castelli, Chiara, additional, Dalerba, Piero, additional, Behroozikhah, Mahdi, additional, Lombardo, Claudia, additional, Novellino, Luisa, additional, Cifola, Ingrid, additional, Casati, Chiara, additional, Longa, Elena Dalla, additional, Schweighoffer, Tamás, additional, Arienti, Flavio, additional, and Parmiani, Giorgio, additional

Published
2022
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32. Identification of the novel HLA‐C allele, HLA‐C*04:520.

Author

Zucchini, Monica, Billiani, Camilla, Mazzocchi, Arabella, Arienti, Flavio, and Taverna, Francesca

Subjects
HISTOCOMPATIBILITY class I antigens, ALLELES, NUCLEOTIDE sequencing
Abstract

HLA‐C*04:520, a novel HLA‐C allele, differs from HLA‐C*04:01:01 by one mismatch in exon 5. [ABSTRACT FROM AUTHOR]

Published
2024
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33. A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-α in metastatic melanoma patients

Author

Pilla, Lorenzo, Patuzzo, Roberto, Rivoltini, Licia, Maio, Michele, Pennacchioli, Elisabetta, Lamaj, Elda, Maurichi, Andrea, Massarut, Samuele, Marchianò, Alfonso, Santantonio, Cristina, Tosi, Diego, Arienti, Flavio, Cova, Agata, Sovena, Gloria, Piris, Adriano, Nonaka, Daisuke, Bersani, Ilaria, Florio, Annabella Di, Luigi, Mariani, Srivastava, Pramod K., Hoos, Axel, Santinami, Mario, and Parmiani, Giorgio

Published
2006
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34. Back to simplicity: a four-marker blood cell score to quantify prognostically relevant myeloid cells in melanoma patients

Author

Huber, Veronica, primary, Di Guardo, Lorenza, additional, Lalli, Luca, additional, Giardiello, Daniele, additional, Cova, Agata, additional, Squarcina, Paola, additional, Frati, Paola, additional, Di Giacomo, Anna Maria, additional, Pilla, Lorenzo, additional, Tazzari, Marcella, additional, Camisaschi, Chiara, additional, Arienti, Flavio, additional, Castelli, Chiara, additional, Rodolfo, Monica, additional, Beretta, Valeria, additional, Di Nicola, Massimo, additional, Maio, Michele, additional, Del Vecchio, Michele, additional, de Braud, Filippo, additional, Mariani, Luigi, additional, and Rivoltini, Licia, additional

Published
2021
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42. Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings

Author

Belli, Filiberto, Testori, Alessandro, Rivoltini, Licia, Maio, Michele, Andreola, Giovanna, Sertoli, Mario Roberto, Gallino, Gianfrancesco, Piris, Adriano, Cattelan, Alessandro, Lazzari, Ivano, Carrabba, Matteo, Scita, Giorgio, Santantonio, Cristina, Pilla, Lorenzo, Tragni, Gabrina, Lombardo, Claudia, Arienti, Flavio, Marchianò, Alfonso, Queirolo, Paola, Bertolini, Francesco, Cova, Agata, Lamaj, Elda, Ascani, Lucio, Camerini, Roberto, Corsi, Marco, Cascinelli, Natale, Lewis, Jonathan J., Srivastava, Pramod, and Parmiani, Giorgio

Published
2002

44. The Real Life Accessibility to CAR T-Cell Therapy: Current Experience in the Only Active Center in Italy

Author

Guidetti, Anna, primary, Perrone, Giulia, additional, Coluccia, Paola, additional, Fumagalli, Luca, additional, Dodero, Anna, additional, Farina, Lucia, additional, Arienti, Flavio, additional, Bagnoli, Filippo, additional, Pappalettera, Luca, additional, Degli Innocenti, Debora, additional, Carniti, Cristiana, additional, Codazzi, Daniela, additional, and Corradini, Paolo, additional

Published
2019
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48. Regression of advanced ovarian carcinoma by intraperitoneal treatment with autologous T lymphocytes retargeted by a bispecific monoclonal antibody

Author

Canevari, Silvana, Stoter, Gerrit, Arienti, Flavio, Bolis, Giorgio, Colnaghi, Maria I., Di Re, Emanuela M., Eggermont, Alexander M.M., Goey, S. Hoo, Gratama, Jan W., Lamers, Cor H.J., Nooy, Marianne A., Parmiani, Giorgio, Raspagliesi, Francesco, Ravagnani, Ferdinando, Scarfone, Giovanna, Trimbos, J. Baptist, Warnaar, Sven O., and Bolhuis, Reinder L.H.

Subjects
Ovarian cancer -- Care and treatment, Cancer regression -- Causes of, T cells -- Health aspects, Monoclonal antibodies -- Health aspects, Health
Abstract

Background: The high frequency of relapse after induction chemotherapy of advanced ovarian carcinoma calls for new therapeutic approaches. Lysis of ovarian carcinoma cells can be achieved by retargeting of T lymphocytes using [F(ab').sub.2] fragments of the bispecific monoclonal antibody (MAb) OC/TR, which is directed to the CD3 molecule on T lymphocytes and to the folate receptor on ovarian carcinoma cells. Purpose: Our purpose was to assess in ovarian carcinoma patients the antitumor activity of in vitro-activated autologous peripheral blood T lymphocytes retargeted with OC/TR. Methods: Patients with epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages III and IV) meeting specific criteria were eligible to enter a phase II immunotherapy trial. Before immunotherapy, the 28 patients who entered the trial underwent laparotomy to reduce their tumor load and to allow measurement of all indicator lesions. They then received two cycles of five daily intraperitoneal infusions of autologous in vitro activated peripheral blood T lymphocytes retargeted with OC/TR plus recombinant interleukin 2 (IL-2) with (n = 11) or without (n = 17) a second daily infusion of OC/TR [F(ab').sub.2] and IL-2. Response to treatment could be assessed in 26 patients following explorative laparotomy; time to progression could be assessed in 27 patients. Results: Seven patients had clinical evidence of progressive disease after treatment and therefore did not undergo laparotomy. Of the 19 patients evaluated by surgery and histology, three showed complete response, one showed complete intraperitoneal response with progressive disease in retroperitoneal lymph nodes, three showed partial response, seven had stable disease, and five had progressive disease. The overall intraperitoneal response rate was 27% (95% confidence interval [CI] = 10%-44%). The complete responses seen in three patients lasted 26 months in one patient, 23 months in the second, and 18 months in the third. Two patients were not assessable for response. One of these patients had bowel perforation during catheter removal, which precluded further evaluation. The second patient was positive only by cytologic examination before immunotherapy, was tumor free at laparotomy after immunotherapy, and remained so for the entire 21 months of follow-up, as determined by cytologic examination of random biopsy specimens. The median time to disease progression in the 15 assessable patients plus those who had stable disease was 11 months (95% CI = 6-18 months). Immunotherapy-related toxic effects included mild to moderate fever, nausea, emesis, and fatigue. Anti-mouse antibodies were detectable by the end of the treatment in 21 of 25 patients tested. Conclusions: Locoregional immunotherapy of ovarian cancer with bi-specific MAb-retargeted T lymphocytes can result in tumor regression. Toxicity was mild to moderate and only transient. Implications: Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.

Published
1995

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