Novel BCMA-OR-CD38 tandem-dual chimeric antigen receptor T cells robustly control multiple myeloma

BCMA-targeting chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against multiple myeloma, yet antigen escape and tumor relapse still occur after the use of these therapies. Designing CAR-T therapies that targets multiple antigens simultaneously seems a feasible way to avoid antigen escape, and it has been extensively studied elsewhere. Here, we report novel BCMA-OR-CD38 Tan CAR T cells that can trigger robust cytotoxicity against target cells expressing either BCMA or CD38. We demonstrate that, in in vitro studies, these BCMA-OR-CD38 Tan CAR T cells exhibit similar CAR expression, superior cytotoxicity and antigen-stimulated T cell proliferation as compared to single-targeted CAR T cells or CD38-OR-BCMA Tan CAR T cells. Importantly, these BCMA-OR-CD38 Tan CAR-T cells can achieve complete tumor clearance in myeloma-bearing mice with no relapse observed through the course of these experiments. Finally, this BCMA-OR-CD38 Tan CAR was fully compatible with existing clinical grade T cell manufacturing procedures and can be implemented using current clinical protocols. Taken together, our results present an effective solution to the challenge of antigen escape in BCMA CAR T-cell therapies.

Automated summary

A novel BCMA-OR-CD38 Tan CAR T cell therapy has been developed, showing potent cytotoxicity against multiple myeloma cells expressing either BCMA or CD38. This therapy demonstrates superior antitumor activity in in vitro studies and successfully clears tumors in myeloma-bearing mice without relapse, providing a promising solution to the challenge of antigen escape in BCMA CAR T-cell therapies.