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1. Hallmarks of Resistance to Immune-Checkpoint InhibitorsHallmarks of Resistance to Immune-Checkpoint Inhibitors

Author

Karasarides, Maria, Cogdill, Alexandria P, Robbins, Paul B, Bowden, Michaela, Burton, Elizabeth M, Butterfield, Lisa H, Cesano, Alessandra, Hammer, Christian, Haymaker, Cara L, Horak, Christine E, McGee, Heather M, Monette, Anne, Rudqvist, Nils-Petter, Spencer, Christine N, Sweis, Randy F, Vincent, Benjamin G, Wennerberg, Erik, Yuan, Jianda, Zappasodi, Roberta, Lucey, Vanessa M Hubbard, Wells, Daniel K, and LaVallee, Theresa

Subjects
Cancer, Good Health and Well Being, Antineoplastic Agents, Immunological, Humans, Immune Checkpoint Inhibitors, Neoplasms, Immunology, Oncology and Carcinogenesis, Pharmacology and Pharmaceutical Sciences
Abstract

Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, biopharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.

Published
2022

2. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2022
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4. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Andrews, Miles C., Duong, Connie P. M., Gopalakrishnan, Vancheswaran, Iebba, Valerio, Chen, Wei-Shen, Derosa, Lisa, Khan, Md Abdul Wadud, Cogdill, Alexandria P., White, Michael G., Wong, Matthew C., Ferrere, Gladys, Fluckiger, Aurélie, Roberti, Maria P., Opolon, Paule, Alou, Maryam Tidjani, Yonekura, Satoru, Roh, Whijae, Spencer, Christine N., Curbelo, Irina Fernandez, Vence, Luis, Reuben, Alexandre, Johnson, Sarah, Arora, Reetakshi, Morad, Golnaz, Lastrapes, Matthew, Baruch, Erez N., Little, Latasha, Gumbs, Curtis, Cooper, Zachary A., Prieto, Peter A., Wani, Khalida, Lazar, Alexander J., Tetzlaff, Michael T., Hudgens, Courtney W., Callahan, Margaret K., Adamow, Matthew, Postow, Michael A., Ariyan, Charlotte E., Gaudreau, Pierre-Olivier, Nezi, Luigi, Raoult, Didier, Mihalcioiu, Catalin, Elkrief, Arielle, Pezo, Rossanna C., Haydu, Lauren E., Simon, Julie M., Tawbi, Hussein A., McQuade, Jennifer, Hwu, Patrick, Hwu, Wen-Jen, Amaria, Rodabe N., Burton, Elizabeth M., Woodman, Scott E., Watowich, Stephanie, Diab, Adi, Patel, Sapna P., Glitza, Isabella C., Wong, Michael K., Zhao, Li, Zhang, Jianhua, Ajami, Nadim J., Petrosino, Joseph, Jenq, Robert R., Davies, Michael A., Gershenwald, Jeffrey E., Futreal, P. Andrew, Sharma, Padmanee, Allison, James P., Routy, Bertrand, Zitvogel, Laurence, and Wargo, Jennifer A.

Published
2021
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6. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2023
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7. Rational development and characterization of humanized anti–EGFR variant III chimeric antigen receptor T cells for glioblastoma

Author

Johnson, Laura A, Scholler, John, Ohkuri, Takayuki, Kosaka, Akemi, Patel, Prachi R, McGettigan, Shannon E, Nace, Arben K, Dentchev, Tzvete, Thekkat, Pramod, Loew, Andreas, Boesteanu, Alina C, Cogdill, Alexandria P, Chen, Taylor, Fraietta, Joseph A, Kloss, Christopher C, Posey, Avery D, Engels, Boris, Singh, Reshma, Ezell, Tucker, Idamakanti, Neeraja, Ramones, Melissa H, Li, Na, Zhou, Li, Plesa, Gabriela, Seykora, John T, Okada, Hideho, June, Carl H, Brogdon, Jennifer L, and Maus, Marcela V

Subjects
Brain Cancer, Gene Therapy, Immunization, Rare Diseases, Human Fetal Tissue, Cancer, Clinical Research, Vaccine Related, Biotechnology, Brain Disorders, Genetics, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Animals, Brain Neoplasms, Disease Models, Animal, ErbB Receptors, Glioblastoma, Heterografts, Humans, Immunotherapy, Mice, Receptors, Antigen, T-Cell, Biological Sciences, Medical and Health Sciences
Abstract

Chimeric antigen receptors (CARs) are synthetic molecules designed to redirect T cells to specific antigens. CAR-modified T cells can mediate long-term durable remissions in B cell malignancies, but expanding this platform to solid tumors requires the discovery of surface targets with limited expression in normal tissues. The variant III mutation of the epidermal growth factor receptor (EGFRvIII) results from an in-frame deletion of a portion of the extracellular domain, creating a neoepitope. We chose a vector backbone encoding a second-generation CAR based on efficacy of a murine scFv-based CAR in a xenograft model of glioblastoma. Next, we generated a panel of humanized scFvs and tested their specificity and function as soluble proteins and in the form of CAR-transduced T cells; a low-affinity scFv was selected on the basis of its specificity for EGFRvIII over wild-type EGFR. The lead candidate scFv was tested in vitro for its ability to direct CAR-transduced T cells to specifically lyse, proliferate, and secrete cytokines in response to antigen-bearing targets. We further evaluated the specificity of the lead CAR candidate in vitro against EGFR-expressing keratinocytes and in vivo in a model of mice grafted with normal human skin. EGFRvIII-directed CAR T cells were also able to control tumor growth in xenogeneic subcutaneous and orthotopic models of human EGFRvIII(+) glioblastoma. On the basis of these results, we have designed a phase 1 clinical study of CAR T cells transduced with humanized scFv directed to EGFRvIII in patients with either residual or recurrent glioblastoma (NCT02209376).

Published
2015

8. Checkpoint Blockade Reverses Anergy in IL-13Rα2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine Gliomas

Author

Yin, Yibo, Boesteanu, Alina C., Binder, Zev A., Xu, Chong, Reid, Reiss A., Rodriguez, Jesse L., Cook, Danielle R., Thokala, Radhika, Blouch, Kristin, McGettigan-Croce, Bevin, Zhang, Logan, Konradt, Christoph, Cogdill, Alexandria P., Panjwani, M. Kazim, Jiang, Shuguang, Migliorini, Denis, Dahmane, Nadia, Posey, Avery D., Jr., June, Carl H., Mason, Nicola J., Lin, Zhiguo, O’Rourke, Donald M., and Johnson, Laura A.

Published
2018
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10. Immunodynamics of explanted human tumors for immuno‐oncology

Author

Dubuisson, Agathe, Fahrner, Jean‐Eudes, Goubet, Anne‐Gaëlle, Terrisse, Safae, Voisin, Nicolas, Bayard, Charles, Lofek, Sebastien, Drubay, Damien, Bredel, Delphine, Mouraud, Séverine, Susini, Sandrine, Cogdill, Alexandria, Rebuffet, Lucas, Ballot, Elise, Jacquelot, Nicolas, Thomas de Montpreville, Vincent, Casiraghi, Odile, Radulescu, Camélia, Ferlicot, Sophie, Figueroa, David J, Yadavilli, Sapna, Waight, Jeremy D, Ballas, Marc, Hoos, Axel, Condamine, Thomas, Parier, Bastien, Gaudillat, Christophe, Routy, Bertrand, Ghiringhelli, François, Derosa, Lisa, Breuskin, Ingrid, Rouanne, Mathieu, André, Fabrice, Lebacle, Cédric, Baumert, Hervé, Wislez, Marie, Fadel, Elie, Cremer, Isabelle, Albiges, Laurence, Geoerger, Birgit, Scoazec, Jean‐Yves, Loriot, Yohann, Kroemer, Guido, Marabelle, Aurélien, Bonvalet, Mélodie, and Zitvogel, Laurence

Published
2021
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13. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

Author

Fraietta, Joseph A., Nobles, Christopher L., Sammons, Morgan A., Lundh, Stefan, Carty, Shannon A., Reich, Tyler J., Cogdill, Alexandria P., Morrissette, Jennifer J. D., DeNizio, Jamie E., Reddy, Shantan, Hwang, Young, Gohil, Mercy, Kulikovskaya, Irina, Nazimuddin, Farzana, Gupta, Minnal, Chen, Fang, Everett, John K., Alexander, Katherine A., Lin-Shiao, Enrique, Gee, Marvin H., Liu, Xiaojun, Young, Regina M., Ambrose, David, Wang, Yan, Xu, Jun, Jordan, Martha S., Marcucci, Katherine T., Levine, Bruce L., Garcia, K. Christopher, Zhao, Yangbing, Kalos, Michael, Porter, David L., Kohli, Rahul M., Lacey, Simon F., Berger, Shelley L., Bushman, Frederic D., June, Carl H., and Melenhorst, J. Joseph

Published
2018
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14. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

Author

Posey, Avery D., Jr., Schwab, Robert D., Boesteanu, Alina C., Steentoft, Catharina, Mandel, Ulla, Engels, Boris, Stone, Jennifer D., Madsen, Thomas D., Schreiber, Karin, Haines, Kathleen M., Cogdill, Alexandria P., Chen, Taylor J., Song, Decheng, Scholler, John, Kranz, David M., Feldman, Michael D., Young, Regina, Keith, Brian, Schreiber, Hans, Clausen, Henrik, Johnson, Laura A., and June, Carl H.

Published
2016
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15. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia

Author

Fraietta, Joseph A., Beckwith, Kyle A., Patel, Prachi R., Ruella, Marco, Zheng, Zhaohui, Barrett, David M., Lacey, Simon F., Melenhorst, Jan Joseph, McGettigan, Shannon E., Cook, Danielle R., Zhang, Changfeng, Xu, Jun, Do, Priscilla, Hulitt, Jessica, Kudchodkar, Sagar B., Cogdill, Alexandria P., Gill, Saar, Porter, David L., Woyach, Jennifer A., Long, Meixiao, Johnson, Amy J., Maddocks, Kami, Muthusamy, Natarajan, Levine, Bruce L., June, Carl H., Byrd, John C., and Maus, Marcela V.

Published
2016
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16. Data from EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib

Author

Corcoran, Ryan B., primary, Ebi, Hiromichi, primary, Turke, Alexa B., primary, Coffee, Erin M., primary, Nishino, Michiya, primary, Cogdill, Alexandria P., primary, Brown, Ronald D., primary, Della Pelle, Patricia, primary, Dias-Santagata, Dora, primary, Hung, Kenneth E., primary, Flaherty, Keith T., primary, Piris, Adriano, primary, Wargo, Jennifer A., primary, Settleman, Jeffrey, primary, Mino-Kenudson, Mari, primary, and Engelman, Jeffrey A., primary

Published
2023
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17. Supplementary Figures 1-9, Table 1, Methods from EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib

Author

Corcoran, Ryan B., primary, Ebi, Hiromichi, primary, Turke, Alexa B., primary, Coffee, Erin M., primary, Nishino, Michiya, primary, Cogdill, Alexandria P., primary, Brown, Ronald D., primary, Della Pelle, Patricia, primary, Dias-Santagata, Dora, primary, Hung, Kenneth E., primary, Flaherty, Keith T., primary, Piris, Adriano, primary, Wargo, Jennifer A., primary, Settleman, Jeffrey, primary, Mino-Kenudson, Mari, primary, and Engelman, Jeffrey A., primary

Published
2023
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18. Supplementary Figure 2 from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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19. Supplementary Figure Legend from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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20. Supplementary Figure 1 from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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21. Supplementary Table 1 from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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22. Supplementary Figure 3 from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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23. Supplementary Table 2 from BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Author

Frederick, Dennie T., primary, Piris, Adriano, primary, Cogdill, Alexandria P., primary, Cooper, Zachary A., primary, Lezcano, Cecilia, primary, Ferrone, Cristina R., primary, Mitra, Devarati, primary, Boni, Andrea, primary, Newton, Lindsay P., primary, Liu, Chengwen, primary, Peng, Weiyi, primary, Sullivan, Ryan J., primary, Lawrence, Donald P., primary, Hodi, F. Stephen, primary, Overwijk, Willem W., primary, Lizée, Gregory, primary, Murphy, George F., primary, Hwu, Patrick, primary, Flaherty, Keith T., primary, Fisher, David E., primary, and Wargo, Jennifer A., primary

Published
2023
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24. Supplementary Figure 2 from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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25. Data from Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice

Author

Liu, Xiaojun, primary, Jiang, Shuguang, primary, Fang, Chongyun, primary, Yang, Shiyu, primary, Olalere, Devvora, primary, Pequignot, Edward C., primary, Cogdill, Alexandria P., primary, Li, Na, primary, Ramones, Melissa, primary, Granda, Brian, primary, Zhou, Li, primary, Loew, Andreas, primary, Young, Regina M., primary, June, Carl H., primary, and Zhao, Yangbing, primary

Published
2023
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26. Supplementary Figure 5 from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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27. Supplementary Figure 3 from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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28. Supplementary Figure 1 from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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29. Supplementary Methods from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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30. Supplementary Figure 4 from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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31. Supplementary Table 1, Figures 1-5 from Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice

Author

Liu, Xiaojun, primary, Jiang, Shuguang, primary, Fang, Chongyun, primary, Yang, Shiyu, primary, Olalere, Devvora, primary, Pequignot, Edward C., primary, Cogdill, Alexandria P., primary, Li, Na, primary, Ramones, Melissa, primary, Granda, Brian, primary, Zhou, Li, primary, Loew, Andreas, primary, Young, Regina M., primary, June, Carl H., primary, and Zhao, Yangbing, primary

Published
2023
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32. Data from Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

Author

Boni, Andrea, primary, Cogdill, Alexandria P., primary, Dang, Ping, primary, Udayakumar, Durga, primary, Njauw, Ching-Ni Jenny, primary, Sloss, Callum M., primary, Ferrone, Cristina R., primary, Flaherty, Keith T., primary, Lawrence, Donald P., primary, Fisher, David E., primary, Tsao, Hensin, primary, and Wargo, Jennifer A., primary

Published
2023
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34. Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration

Author

Zhou, Yifan, primary, Medik, Yusra B., additional, Patel, Bhakti, additional, Zamler, Daniel B., additional, Chen, Sijie, additional, Chapman, Thomas, additional, Schneider, Sarah, additional, Park, Elizabeth M., additional, Babcock, Rachel L., additional, Chrisikos, Taylor T., additional, Kahn, Laura M., additional, Dyevoich, Allison M., additional, Pineda, Josue E., additional, Wong, Matthew C., additional, Mishra, Aditya K., additional, Cass, Samuel H., additional, Cogdill, Alexandria P., additional, Johnson, Daniel H., additional, Johnson, Sarah B., additional, Wani, Khalida, additional, Ledesma, Debora A., additional, Hudgens, Courtney W., additional, Wang, Jingjing, additional, Wadud Khan, Md Abdul, additional, Peterson, Christine B., additional, Joon, Aron Y., additional, Peng, Weiyi, additional, Li, Haiyan S., additional, Arora, Reetakshi, additional, Tang, Ximing, additional, Raso, Maria Gabriela, additional, Zhang, Xuegong, additional, Foo, Wai Chin, additional, Tetzlaff, Michael T., additional, Diehl, Gretchen E., additional, Clise-Dwyer, Karen, additional, Whitley, Elizabeth M., additional, Gubin, Matthew M., additional, Allison, James P., additional, Hwu, Patrick, additional, Ajami, Nadim J., additional, Diab, Adi, additional, Wargo, Jennifer A., additional, and Watowich, Stephanie S., additional

Published
2022
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37. Abstract 5545: Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration

Author

Zhou, Yifan, primary, Medik, Yusra B., additional, Patel, Bhakti, additional, Zamler, Daniel B., additional, Chen, Sijie, additional, Chapman, Thomas, additional, Schneider, Sarah, additional, Babcock, Rachel L., additional, Chrisikos, Taylor T., additional, Kahn, Laura M., additional, Dyevoich, Allison M., additional, Park, Elizabeth M., additional, Cogdill, Alexandria P., additional, Johnson, Daniel H., additional, Johnson, Sarah B., additional, Wani, Khalida M., additional, Ledesma, Debora A., additional, Hudgens, Courtney W., additional, Wang, Jingjing, additional, Khan, Md Abdul Wadud, additional, Joon, Aron Y., additional, Peng, Weiyi, additional, Li, Haiyan S., additional, Arora, Reetakshi, additional, Tang, Ximing, additional, Raso, Maria Gabriela, additional, Zhang, Xuegong, additional, Foo, Wai Chin, additional, Tetzlaff, Michael T., additional, Diehl, Gretchen E., additional, Clise-Dwyer, Karen, additional, Whitley, Elizabeth M., additional, Gubin, Matthew M., additional, Allison, James P., additional, Hwu, Patrick, additional, Ajami, Nadim J., additional, Diab, Adi, additional, Wargo, Jennifer A., additional, and Watowich, Stephanie S., additional

Published
2022
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38. Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma

Author

Reuben, Alexandre, Spencer, Christine N., Prieto, Peter A., Gopalakrishnan, Vancheswaran, Reddy, Sangeetha M., Miller, John P., Mao, Xizeng, De Macedo, Mariana Petaccia, Chen, Jiong, Song, Xingzhi, Jiang, Hong, Chen, Pei-Ling, Beird, Hannah C., Garber, Haven R., Roh, Whijae, Wani, Khalida, Chen, Eveline, Haymaker, Cara, Forget, Marie-Andrée, Little, Latasha D., Gumbs, Curtis, Thornton, Rebecca L., Hudgens, Courtney W., Chen, Wei-Shen, Austin-Breneman, Jacob, Sloane, Robert Szczepaniak, Nezi, Luigi, Cogdill, Alexandria P., Bernatchez, Chantale, Roszik, Jason, Hwu, Patrick, Woodman, Scott E., Chin, Lynda, Tawbi, Hussein, Davies, Michael A., Gershenwald, Jeffrey E., Amaria, Rodabe N., Glitza, Isabella C., Diab, Adi, Patel, Sapna P., Hu, Jianhua, Lee, Jeffrey E., Grimm, Elizabeth A., Tetzlaff, Michael T., Lazar, Alexander J., Wistuba, Ignacio I., Clise-Dwyer, Karen, Carter, Brett W., Zhang, Jianhua, Futreal, P. Andrew, Sharma, Padmanee, Allison, James P., Cooper, Zachary A., and Wargo, Jennifer A.

Published
2017
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39. Hallmarks of Resistance to Immune-Checkpoint Inhibitors.

Author

Karasarides, Maria, Karasarides, Maria, Cogdill, Alexandria P, Robbins, Paul B, Bowden, Michaela, Burton, Elizabeth M, Butterfield, Lisa H, Cesano, Alessandra, Hammer, Christian, Haymaker, Cara L, Horak, Christine E, McGee, Heather M, Monette, Anne, Rudqvist, Nils-Petter, Spencer, Christine N, Sweis, Randy F, Vincent, Benjamin G, Wennerberg, Erik, Yuan, Jianda, Zappasodi, Roberta, Lucey, Vanessa M Hubbard, Wells, Daniel K, LaVallee, Theresa, Karasarides, Maria, Karasarides, Maria, Cogdill, Alexandria P, Robbins, Paul B, Bowden, Michaela, Burton, Elizabeth M, Butterfield, Lisa H, Cesano, Alessandra, Hammer, Christian, Haymaker, Cara L, Horak, Christine E, McGee, Heather M, Monette, Anne, Rudqvist, Nils-Petter, Spencer, Christine N, Sweis, Randy F, Vincent, Benjamin G, Wennerberg, Erik, Yuan, Jianda, Zappasodi, Roberta, Lucey, Vanessa M Hubbard, Wells, Daniel K, and LaVallee, Theresa

Abstract

Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, biopharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.

Published
2022

40. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, C, White, M, Andrews, M, Chelvanambi, M, Witt, R, Daniele, J, Titus, M, Mcquade, J, Conforti, F, Burton, E, Lastrapes, M, Ologun, G, Cogdill, A, Morad, G, Prieto, P, Lazar, A, Chu, Y, Han, G, Khan, M, Helmink, B, Davies, M, Amaria, R, Kovacs, J, Woodman, S, Patel, S, Hwu, P, Peoples, M, Lee, J, Cooper, Z, Zhu, H, Gao, G, Banerjee, H, Lau, M, Gershenwald, J, Lucci, A, Keung, E, Ross, M, Pala, L, Pagan, E, Segura, R, Liu, Q, Borthwick, M, Lau, E, Yates, M, Westin, S, Wani, K, Tetzlaff, M, Haydu, L, Mahendra, M, Ma, X, Logothetis, C, Kulstad, Z, Johnson, S, Hudgens, C, Feng, N, Federico, L, Long, G, Futreal, P, Arur, S, Tawbi, H, Moran, A, Wang, L, Heffernan, T, Marszalek, J, Wargo, J, Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., Wargo, Jennifer A., Vellano, C, White, M, Andrews, M, Chelvanambi, M, Witt, R, Daniele, J, Titus, M, Mcquade, J, Conforti, F, Burton, E, Lastrapes, M, Ologun, G, Cogdill, A, Morad, G, Prieto, P, Lazar, A, Chu, Y, Han, G, Khan, M, Helmink, B, Davies, M, Amaria, R, Kovacs, J, Woodman, S, Patel, S, Hwu, P, Peoples, M, Lee, J, Cooper, Z, Zhu, H, Gao, G, Banerjee, H, Lau, M, Gershenwald, J, Lucci, A, Keung, E, Ross, M, Pala, L, Pagan, E, Segura, R, Liu, Q, Borthwick, M, Lau, E, Yates, M, Westin, S, Wani, K, Tetzlaff, M, Haydu, L, Mahendra, M, Ma, X, Logothetis, C, Kulstad, Z, Johnson, S, Hudgens, C, Feng, N, Federico, L, Long, G, Futreal, P, Arur, S, Tawbi, H, Moran, A, Wang, L, Heffernan, T, Marszalek, J, Wargo, J, Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Abstract

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.021). The findings were validated in several additional cohorts2–4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P = 0.0006 and P = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P = 0.018 and P = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P = 0.021 and P < 0.0001). Together, these results have important implications for therapy.

Published
2022

41. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response

Author

Spencer, Christine N., primary, McQuade, Jennifer L., additional, Gopalakrishnan, Vancheswaran, additional, McCulloch, John A., additional, Vetizou, Marie, additional, Cogdill, Alexandria P., additional, Khan, Md A. Wadud, additional, Zhang, Xiaotao, additional, White, Michael G., additional, Peterson, Christine B., additional, Wong, Matthew C., additional, Morad, Golnaz, additional, Rodgers, Theresa, additional, Badger, Jonathan H., additional, Helmink, Beth A., additional, Andrews, Miles C., additional, Rodrigues, Richard R., additional, Morgun, Andrey, additional, Kim, Young S., additional, Roszik, Jason, additional, Hoffman, Kristi L., additional, Zheng, Jiali, additional, Zhou, Yifan, additional, Medik, Yusra B., additional, Kahn, Laura M., additional, Johnson, Sarah, additional, Hudgens, Courtney W., additional, Wani, Khalida, additional, Gaudreau, Pierre-Olivier, additional, Harris, Angela L., additional, Jamal, Mohamed A., additional, Baruch, Erez N., additional, Perez-Guijarro, Eva, additional, Day, Chi-Ping, additional, Merlino, Glenn, additional, Pazdrak, Barbara, additional, Lochmann, Brooke S., additional, Szczepaniak-Sloane, Robert A., additional, Arora, Reetakshi, additional, Anderson, Jaime, additional, Zobniw, Chrystia M., additional, Posada, Eliza, additional, Sirmans, Elizabeth, additional, Simon, Julie, additional, Haydu, Lauren E., additional, Burton, Elizabeth M., additional, Wang, Linghua, additional, Dang, Minghao, additional, Clise-Dwyer, Karen, additional, Schneider, Sarah, additional, Chapman, Thomas, additional, Anang, Nana-Ama A. S., additional, Duncan, Sheila, additional, Toker, Joseph, additional, Malke, Jared C., additional, Glitza, Isabella C., additional, Amaria, Rodabe N., additional, Tawbi, Hussein A., additional, Diab, Adi, additional, Wong, Michael K., additional, Patel, Sapna P., additional, Woodman, Scott E., additional, Davies, Michael A., additional, Ross, Merrick I., additional, Gershenwald, Jeffrey E., additional, Lee, Jeffrey E., additional, Hwu, Patrick, additional, Jensen, Vanessa, additional, Samuels, Yardena, additional, Straussman, Ravid, additional, Ajami, Nadim J., additional, Nelson, Kelly C., additional, Nezi, Luigi, additional, Petrosino, Joseph F., additional, Futreal, P. Andrew, additional, Lazar, Alexander J., additional, Hu, Jianhua, additional, Jenq, Robert R., additional, Tetzlaff, Michael T., additional, Yan, Yan, additional, Garrett, Wendy S., additional, Huttenhower, Curtis, additional, Sharma, Padmanee, additional, Watowich, Stephanie S., additional, Allison, James P., additional, Cohen, Lorenzo, additional, Trinchieri, Giorgio, additional, Daniel, Carrie R., additional, and Wargo, Jennifer A., additional

Published
2021
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42. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen

Author

Johnson, Laura A., Morgan, Richard A., Dudley, Mark E., Cassard, Lydie, Yang, James C., Hughes, Marybeth S., Kammula, Udai S., Royal, Richard E., Sherry, Richard M., Wunderlich, John R., Lee, Chyi-Chia R., Restifo, Nicholas P., Schwarz, Susan L., Cogdill, Alexandria P., Bishop, Rachel J., Kim, Hung, Brewer, Carmen C., Rudy, Susan F., VanWaes, Carter, Davis, Jeremy L., Mathur, Aarti, Ripley, Robert T., Nathan, Debbie A., Laurencot, Carolyn M., and Rosenberg, Steven A.

Published
2009
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43. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation

Author

Johannessen, Cory M., Boehm, Jesse S., Kim, So Young, Thomas, Sapana R., Wardwell, Leslie, Johnson, Laura A., Emery, Caroline M., Stransky, Nicolas, Cogdill, Alexandria P., Barretina, Jordi, Caponigro, Giordano, Hieronymus, Haley, Murray, Ryan R., Salehi-Ashtiani, Kourosh, Hill, David E., Vidal, Marc, Zhao, Jean J., Yang, Xiaoping, Alkan, Ozan, Kim, Sungjoon, Harris, Jennifer L., Wilson, Christopher J., Myer, Vic E., Finan, Peter M., Root, David E., Roberts, Thomas M., Golub, Todd, Flaherty, Keith T., Dummer, Reinhard, Weber, Barbara L., Sellers, William R., Wargo, Jennifer A., Hahn, William C., and Garraway, Levi A.

Subjects
Research, Properties, Protein research -- Research, Cancer cells -- Properties -- Research, Cell lines -- Research, Protein kinases -- Properties -- Research
Abstract

To identify kinases capable of circumventing RAF inhibition, we assembled and stably expressed 597 sequence-validated kinase ORF clones representing ~75% of annotated kinases (Center for Cancer Systems Biology (CCSB)/Broad Institute [...], Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas (1). Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma (2-6)--an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials (7-9) However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance (10-12). Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies (13). Here we expressed ~600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.

Published
2010
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44. Immunodynamics of explanted human tumors for immuno‐oncology

Author

Dubuisson, Agathe, Fahrner, Jean Eudes, Goubet, Anne Gaëlle, Terrisse, Safae A., Voisin, Nicolas, Bayard, Charles, Lofek, Sébastien, Drubay, Damien, Bredel, Delphine, Mouraud, Séverine, Susini, Sandrine, Cogdill, Alexandria P., Rebuffet, Lucas, Ballot, Elise, Jacquelot, Nicolas, Thomas de Montpreville, Vincent, Casiraghi, Odile, Radulescu, Camélia, Ferlicot, Sophie, Figueroa, David J., Yadavilli, Sapna, Waight, Jeremy D., Ballas, Marc S., Hoos, Axel X., Condamine, Thomas, Parier, Bastien, Gaudillat, Christophe, Routy, Bertrand, Ghiringhelli, François, Derosa, Lisa, Breuskin, Ingrid, Rouanne, Mathieu, André, Fabrice, Lebacle, Cédric, Baumert, Hervé, Wislez, Marie, Fadel, Élie, Cremer, Isabelle, Albiges, Laurence, Geoerger, Birgit, Scoazec, Jean Yves, Loriot, Yohann, Kroemer, Guido, Marabelle, Aurélien, Bonvalet, Mélodie, Zitvogel, Laurence, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), The University of Texas M.D. Anderson Cancer Center [Houston], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, The Walter and Eliza Hall Institute of Medical Research (WEHI), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de médecine oncologique [Gustave Roussy], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Direction de la recherche [Gustave Roussy], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska University Hospital [Stockholm], Chancellerie des Universités de Paris Agence Nationale de la Recherche, ANR Seerave Foundation Association pour la Recherche sur le Cancer, ARC ANR‐16‐RHUS‐0008 Ligue Contre le Cancer European Commission, EC Fondation pour la Recherche Médicale, FRM Institut National Du Cancer, INCa Institut Universitaire de France, IUF European Research Council, ERC Fondation Leducq RP170067 Association pour la Recherche sur le Cancer, ARC, LZ and GK were supported by the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR) francogermanique ANR‐19‐CE15‐0029, ANR Projects blancs, ANR under the frame of E‐Rare‐2, the ERA‐Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Bristol‐Myers Squibb Company (International Immuno‐Oncology Network), Cancéropôle Ile‐de‐France, Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM), a donation by Elior, the European Commission (ArtForce), the European Research Council (ERC), Fondation Carrefour, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno‐Oncology, the RHU Torino Lumière (ANR‐16‐RHUS‐0008), H2020 ONCOBIOME, the Seerave Foundation, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), FHU CARE, Dassault, and Badinter Philantropia, and the Paris Alliance of Cancer Research Institutes (PACRI). AC is supported by the CPRIT Research Training Program (RP170067). JEF was supported by Transgene and AGG was supported by FRM. AM has been or is currently an investigator in clinical trials sponsored by BMS, MSD, GSK/Tesaro, Janssen, Roche/Genentech, Pfizer, Astra Zeneca (AZ), Amgen. AM has been or is currently a member of Clinical Trial Scientific Steering Committee for AZ and GSK. AM has been or is currently a member of the scientific advisory board of the following companies: Merck Serono, Novartis, BMS, Symphogen, Amgen, Tesaro/GSK, Pfizer, Astra Zeneca/Medimmune, Servier, Sanofi. AM has provided Scientific & Medical Consulting to the following companies: Roche, Sanofi. AM is a member of the Data Safety and Monitoring Board for the following trial NCT02423863 (TLR3 agonist, Oncovir). AM has received research funding and or drug supply for pre‐Clinical and clinical research projects from: BMS, Boehringer Ingelheim, Idera, MSD, Fondation MSD Avenir, SIRIC (INCa‐DGOS‐Inserm_12551)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)

Subjects
Medicine (General), [SDV]Life Sciences [q-bio], Immunology, QH426-470, Medical Oncology, immune checkpoint inhibitors, R5-920, immunomonitoring, Report, precision oncology, Neoplasms, Genetics, “in sitro” assay, Tumor Microenvironment, cancer, Humans, Immunotherapy, Prospective Studies, Reports
Abstract

Decision making in immuno‐oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno‐assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti‐PD‐1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay., To predict cancer resistance to PD‐1 blockade and design suitable combinations of immunomodulators, a 60‐h functional in sitro assay was set up in 43 tumors that allowed calculation of the “Immune Reactivity Score (IRS)” based on 17 TCR‐dependent‐ cytokines/chemokines.

Published
2020
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45. The human tumor microbiome is composed of tumor type–specific intracellular bacteria

Author

Nejman, Deborah, primary, Livyatan, Ilana, additional, Fuks, Garold, additional, Gavert, Nancy, additional, Zwang, Yaara, additional, Geller, Leore T., additional, Rotter-Maskowitz, Aviva, additional, Weiser, Roi, additional, Mallel, Giuseppe, additional, Gigi, Elinor, additional, Meltser, Arnon, additional, Douglas, Gavin M., additional, Kamer, Iris, additional, Gopalakrishnan, Vancheswaran, additional, Dadosh, Tali, additional, Levin-Zaidman, Smadar, additional, Avnet, Sofia, additional, Atlan, Tehila, additional, Cooper, Zachary A., additional, Arora, Reetakshi, additional, Cogdill, Alexandria P., additional, Khan, Md Abdul Wadud, additional, Ologun, Gabriel, additional, Bussi, Yuval, additional, Weinberger, Adina, additional, Lotan-Pompan, Maya, additional, Golani, Ofra, additional, Perry, Gili, additional, Rokah, Merav, additional, Bahar-Shany, Keren, additional, Rozeman, Elisa A., additional, Blank, Christian U., additional, Ronai, Anat, additional, Shaoul, Ron, additional, Amit, Amnon, additional, Dorfman, Tatiana, additional, Kremer, Ran, additional, Cohen, Zvi R., additional, Harnof, Sagi, additional, Siegal, Tali, additional, Yehuda-Shnaidman, Einav, additional, Gal-Yam, Einav Nili, additional, Shapira, Hagit, additional, Baldini, Nicola, additional, Langille, Morgan G. I., additional, Ben-Nun, Alon, additional, Kaufman, Bella, additional, Nissan, Aviram, additional, Golan, Talia, additional, Dadiani, Maya, additional, Levanon, Keren, additional, Bar, Jair, additional, Yust-Katz, Shlomit, additional, Barshack, Iris, additional, Peeper, Daniel S., additional, Raz, Dan J., additional, Segal, Eran, additional, Wargo, Jennifer A., additional, Sandbank, Judith, additional, Shental, Noam, additional, and Straussman, Ravid, additional

Published
2020
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47. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

Author

Posey, Avery D, Schwab, Robert D, Boesteanu, Alina C, Steentoft, Catharina, Mandel, Ulla, Engels, Boris, Stone, Jennifer D, Madsen, Thomas D, Schreiber, Karin, Haines, Kathleen M, Cogdill, Alexandria P, Chen, Taylor J, Song, Decheng, Scholler, John, Kranz, David M, Feldman, Michael D, Young, Regina, Keith, Brian, Schreiber, Hans, Clausen, Henrik, Johnson, Laura A, June, Carl H, Posey, Avery D, Schwab, Robert D, Boesteanu, Alina C, Steentoft, Catharina, Mandel, Ulla, Engels, Boris, Stone, Jennifer D, Madsen, Thomas D, Schreiber, Karin, Haines, Kathleen M, Cogdill, Alexandria P, Chen, Taylor J, Song, Decheng, Scholler, John, Kranz, David M, Feldman, Michael D, Young, Regina, Keith, Brian, Schreiber, Hans, Clausen, Henrik, Johnson, Laura A, and June, Carl H

Abstract

Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.

Published
2016

49. Abstract B139: Toxicity testing of EGFRvIII CAR-based immunotherapy of glioblastoma: From bench to bedside

Author

Cogdill, Alexandria P., primary, Boesteanu, Alina, additional, Xu, Chong, additional, Haines, Kathleen, additional, Scholler, John, additional, Fraietta, Joseph, additional, Zhao, Yangbing, additional, Liu, Xiaojun, additional, Morrissette, Jennifer, additional, Levine, Bruce, additional, Lacey, Simon, additional, Loew, Andreas, additional, Singh, Reshma, additional, Brogdon, Jennifer, additional, O'Rourke, Donald M., additional, Maus, Marcela V., additional, June, Carl H., additional, and Johnson, Laura A., additional

Published
2016
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50. Abstract B05: A biologic screen to evaluate potential toxicity of chimeric antigen receptor modified T cells against primary normal human tissues

Author

Cogdill, Alexandria P., primary, Boesteanu, Alina, additional, Haines, Kathleen, additional, Fraietta, Joseph, additional, Scholler, John, additional, Loew, Andreas, additional, Thekkat, Pramod, additional, Brogdon, Jennifer, additional, Maus, Marcela V., additional, June, Carl, additional, and Johnson, Laura A., additional

Published
2015
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