A second‐generation CD38‐CAR‐T cell for the treatment of multiple myeloma

BACKGROUND: Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T‐cell therapy has been a promising immunotherapy against hematological malignancies. METHODS: In this study, we developed a second‐generation CAR construct and generated CAR‐T cells targeting CD38 molecule. Then effects of CAR‐T cells against MM cell lines were evaluated. RESULTS: CD38‐CAR‐T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR‐T cells even at effector to target ratio of 1:100. CAR‐T cells also showed an enhanced cytotoxicity against primary MM cells. CAR‐T cells could be activated and produced a variety of cytokines in a target‐dependent manner. In vivo test indicated that CAR‐T cells also showed significant antitumor effect on xenograft mice models. CONCLUSION: These results indicated a promising therapeutic strategy of CD38‐CAR‐T cells against MM.