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13. Challenges and next steps in the advancement of immunotherapy: summary of the 2018 and 2020 National Cancer Institute workshops on cell-based immunotherapy for solid tumors

Author

Nirali Shah, Lili Yang, Anju Singh, Kasia Bourcier, Antoni Ribas, Pawel Kalinski, Ke Liu, Phil Greenberg, Carl June, Marcela Maus, Steven Rosenberg, Madhav Dhodapkar, Irina Tiper, Chantale Bernatchez, Michael Hudecek, Stanley Riddell, Stephen Gottschalk, Crystal Mackall, Lisa Butterfield, Greg Delgoffe, Michael Nishimura, Terry Fry, Marc S. Ernstoff, Christopher Klebanoff, Elad Sharon, Malcolm Brenner, Cliona Rooney, Christine Brown, Marc S Ernstoff, Tonya Webb, Magdalena Thurin, Wendell Lim, David Stroncek, Catherine Bollard, Helen Chen, Cameron Turtle, Christian Hinrichs, Laura K Fogli, Rosemarie Aurigemma, Connie L Sommers, Steven Albelda, Renier Brentjens, Yvonne Chen, Laronna Colbert, Kenneth Cornetta, Jason Cristofaro, Thomas Finn, Laura K Fogli Hunter, Alyssa Galaro, Ananda Goldrath, Ray Harris, Lori Henderson, Yuxia Jia, Dan Kaufman, Bruce Levine, Lawrence Lum, Samantha Maragh, Alex Marson, Raj Puri, Jake Reder, Kole Roybal, Rachelle Salomon, Tal Salz, Barbra Sasu, Andrea Schietinger, Connie L. Sommers, Minkyung Song, Fyodor Urnov, Anthony Welch, Travis Young, and Jason Yovandich

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Cell-based immunotherapies have had remarkable success in the clinic, specifically in the treatment of hematologic malignancies. However, these strategies have had limited efficacy in patients with solid tumors. To better understand the challenges involved, the National Cancer Institute (NCI) convened an initial workshop with immuno-oncology thought leaders in December 2018 and a follow-up workshop in December 2020. The goals of the NCI workshops on cell-based immunotherapy for solid tumors were to discuss the current state of the field of cell-based immunotherapy, obtain insights into critical knowledge gaps, and identify ways in which NCI could facilitate progress. At both meetings, subjects emphasized four main types of challenges in further developing cell-based immunotherapy for patients with solid tumors: scientific, technical, clinical, and regulatory. The scientific barriers include selecting appropriate targets, ensuring adequate trafficking of cell therapy products to tumor sites, overcoming the immunosuppressive tumor microenvironment, and identifying appropriate models for these investigations. While mouse models may provide some useful data, the majority of those that are commonly used are immunodeficient and unable to fully recapitulate the immune response in patients. There is therefore a need for enhanced support of small early-phase human clinical studies, preferably with adaptive trial designs, to provide proof of concept for novel cell therapy approaches. Furthermore, the requirements for manufacturing, shipping, and distributing cell-based therapies present technical challenges and regulatory questions, which many research institutions are not equipped to address. Overall, workshop subjects identified key areas where NCI support might help the research community in driving forward innovation and clinical utility: 1) provide focused research support on topics such as tumor target selection, immune cell fitness and persistence, cell trafficking, and the immunosuppressive tumor microenvironment; 2) support the rapid translation of preclinical findings into proof of concept clinical testing, harmonize clinical trial regimens, and facilitate early trial data sharing (including negative results); 3) expand manufacturing support for cell therapies, including vectors and reagents, and provide training programs for technical staff; and 4) develop and share standard operating procedures for cell handling and analytical assays, and work with the Food and Drug Administration to harmonize product characterization specifications.

Published
2021
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14. 254 CTLA-4 blockade promotes Treg glucose metabolism and reduces Treg functional stability in glycolysis-defective tumors

Author

Yasin Senbabaoglu, Greg Delgoffe, Ping-Chih Ho, Arnab Ghosh, Svena Verma, McLane Watson, Inna Serganova, Ivan Cohen, Masatomo Maeda, Masahiro Shindo, Rachana Maniyar, Mayuresh Mane, Avigdor Leftin, Matthew Lubin, Myat Kyaw Ko, Mohsen Abu-Akeel, Ellen Ackerstaff, Jason Koutcher, and Ronald Blasberg

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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