Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer.

ABSTRACT: The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression of chimeric antigen receptors (CARs) has produced tumor responses, even in patients with refractory diseases. To target pancreatic cancer, we generated CAR T cells directed against prostate stem cell antigen (PSCA) and demonstrated specific tumor lysis. However, pancreatic tumors employ immune evasion strategies such as the production of inhibitory cytokines, which limit CAR T cell persistence and function. Thus, to protect our cells from the immunosuppressive cytokine IL-4, we generated an inverted cytokine receptor in which the IL-4 receptor exodomain was fused to the IL-7 receptor endodomain (4/7 ICR). Transgenic expression of this molecule in CAR-PSCA T cells should invert the inhibitory

SUBMITTER: Mohammed S 

PROVIDER: S-EPMC5363304 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature