Tumor-Derived Extracellular Vesicles Impair CD171-Specific CD4⁺ CAR T Cell Efficacy.

ABSTRACT: Chimeric antigen receptor (CAR) T cell efficacy against solid tumors is currently limited by several immune escape mechanisms, which may include tumor-derived extracellular vesicles. Advanced neuroblastoma is an aggressive childhood tumor without curative treatment options for most relapsed patients today. We here evaluated the role of tumor-derived extracellular vesicles on the efficacy of CAR T cells targeting the neuroblastoma-specific antigen, CD171. For this purpose, CAR T cell activation, cytokine production, exhaustion, and tumor cell-directed cytotoxicity upon co-culture was evaluated. Tumor-derived extracellular vesicles isolated from SH-SY5Y neuroblastoma cells neither affected CAR T cell activation nor expression of inhibitory markers. Importantly, exposure of CD4⁺ CD

SUBMITTER: Ali S 

PROVIDER: S-EPMC7137471 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature