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

Abstract

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.