Sensitizing solid tumors to respond to Cytokine-induced apoptosis and CAR T-cell therapy.

Abstract Chimeric antigen receptor (CAR) T-cells are engineered with synthetic receptors that directs their specificity and function toward an of choice. This application has been highly successful in treating a variety blood-borne cancers such as B-cell lymphomas. CAR against solid tumors have less efficacious, potentially due to the resistance tumor cells T cell-mediated cytotoxicity. Current paradigm suggests killed by perforin/granzyme-secreting CD8 cytotoxic (CTLs). However, activated also produce TNF IFNg, two cytokines reported anti-tumor function, but it is not clear whether these can directly kill targets. It defects kinases TNFR1 signaling pathway sensitize TNF-induced death. Therefore, we hypothesize inactivating kinases, killing producing IFNg. We intend conduct proof-of-concept studies show sensitizing cytokine-mediated cytotoxicity will enhance effectiveness T-cell therapy tumors. Institutional Funding