V gamma 9V delta 2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth

V gamma 9V delta 2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of V gamma 9V delta 2 T cells, we introduced a BCMA-specific CAR into ex vivo expanded V gamma 9V delta 2 T cells through electroporation of the CAR-encoding mRNA. The modified V gamma 9V delta 2 T cells displayed a high cytolytic activity against BCMA-expressing MM cell lines in vitro, while sparing BCMA-negative cells, including normal B cells and monocytes. Subsequently, we intravenously injected KMS-11 human MM cells to generate a xenograft mouse model. The treatment of the tumor-bearing mice with Zometa and anti-BCMA CAR- V gamma 9V delta 2 T cells resulted in a significant reduction of tumor burden in the femur region, as well as the overall tumor burden. In association with the decrease in tumor burden, the survival of the MM cell-inoculated mice was markedly prolonged. Considering the potential of V gamma 9V delta 2 T cells to be used as off-the-shelf products, the modification of these cells with a BCMA-specific CAR could be an attractive option for cancer immunotherapy against bone marrow cancer MM.