Joshua Brody MD Director, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine New York, New York 10029

Icahn Researchers Find Cancer Immunotherapy Improved When Bystander Cells Killed

MedicalResearch.com Interview with:

Joshua Brody MD Director, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine New York, New York 10029

Dr. Brody

Joshua Brody MD
Director, Lymphoma Immunotherapy Program
Icahn School of Medicine at Mount Sinai
Hess Center for Science and Medicine
New York, New York 10029

MedicalResearch.com: What is the background for this study?

Response: Cancer Immunotherapies target “antigens” on the surface of cells.

-CAR-T cells targets antigens e.g. CD19
-Bispecific antibodies target antigens e.g. CD20
-Anti-PD1 antibodies awaken T cells that target antigens on e.g. MHC-I

Cancer Immunotherapies frequently fail because a small percent of tumor cells simply lack the antigen and cause cancer relapse (‘Antigen Escape’)

MedicalResearch.com: What are the main findings?

Response: T cells mobilized to kill cancer (CAR-, bispecific-, or anti-PD1-mobilized) can kill both the ‘Target’ tumor as well as immediately adjacent (‘Bystander’) tumor cells that lack the antigen by activating tumor cell ‘fas’ protein.

Bystander tumor cell killing may already be preventing some patients from Antigen Escape cancer relapse.

Some targeted cancer therapies already being used can increase fas signaling and thereby increase Bystander killing and likely reduce the risk of relapse after immunotherapy.

MedicalResearch.com: Does the killing of bystander cells explain some of the side effects of immunotherapy?

Response: No, it does not seem so, because only geographically localized (e.g. immediately adjacent) cells are killed by bystander killing.

MedicalResearch.com: What should readers take away from your report?

Response: A common type of resistance to cancer immunotherapy (Antigen Escape) can likely be prevented.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: There are several easily initiated clinical trials combining targeted therapies that increase fas-signaling with immunotherapies to improve remission durations.

Disclosures: Brody Lab receives support from: Kite/Gilead, Genentech, Acerta, Celgene, Seattle Genetics, BMS, Merck

Citation:

A critical role for fas-mediated off-target tumor killing in T cell immunotherapy

Ranjan Upadhyay, Jonathan A. Boiarsky, Gvantsa Pantsulaia, Judit Svensson-Arvelund, Matthew J. Lin, Aleksandra Wroblewska, Sherry Bhalla, Nathalie Scholler, Adrian Bot, John M Rossi, Norah Sadek, Samir Parekh, Alessia Baccarini, Miriam Merad, Brian D Brown and Joshua D Brody

Cancer Discovery December 17 2020 DOI:10.1158/2159-8290.CD-20-0756

Dec 17, 2020 @ 4:25 pm

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