CAR T Cell Cytotoxicity Is Dependent on Death Receptor-Driven Apoptosis

Conclusions: CART19 can cure select patients with B-cell cancers, while others experience transient or no clinical benefit. Using a genome-wide loss of function screen, we identified that death receptor-associated proteins are centrally involved in regulating CART19 cytotoxicity, and that loss of these molecules leads to intrinsic resistance to CART19. These findings are, to our knowledge, the first to characterize the role of death receptors as critical regulators of CART19 cytotoxicity, and suggest that tumor cell modulation of death receptor signaling may drive both inherent resistance and antigen-independent relapse.DisclosuresJune: Celldex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceutical Corporation: Patents & Royalties, Research Funding; Immune Design: Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Novartis Pharmaceutical Corporation: Patents & Royalties, Research Funding; Immune Design: Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Gill: Novartis: Research Funding; Carisma Therapeutics: Equity Ownership; Extellia: Consultancy, Membership on an entity's Board of ...

Source: Blood - November 21, 2018 Category: Hematology Authors: Singh, N., Shestova, O., Hayer, K., Hong, A., Ravikumar, P., Hoshino, A., Shalem, O., Weitzman, M. D., June, C. H., Gill, S. I., Ruella, M. Tags: 703. Adoptive Immunotherapy: In Vitro, Correlative, and Early Phase Studies to Improve Safety and Efficacy of CAR-T Cells Source Type: research