Divergent on-target off-tumor effects by CAR T and CAR NK cells suggest different efficacy and safety of cell therapies.

ABSTRACT: CAR-based cell therapies have shown clinical success in treating various cancers, with CAR T cell therapies entering the clinical route and CAR NK cell therapies being evaluated in early-stage clinical trials. A key challenge is the presence of tumor-associated antigens on healthy cells, risking on-target off-tumor toxicities. Our comparative analysis of CAR T and CAR NK cells targeting the multiple myeloma-associated antigens BCMA, SLAMF7, and CD38 revealed that antigen density on target cells significantly modulates CAR NK cell activation and cytotoxicity. The cytotoxic potential of CAR NK cells was comparable to that of CAR T cells when targeting BCMA and CD38, but notable differences were observed in SLAMF7-directed CAR cells. While CAR sensitivity was similar in both cell types, CAR N

SUBMITTER: Schindler-Wnek K 

PROVIDER: S-EPMC12416173 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature