A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of V gamma 9V delta 2 T cells

Aim: To investigate whether anti-CD123 chimeric antigen receptor (CAR)-expressing V gamma 9V delta 2 T cells could be an alternative for acute myeloid leukemia (AML) treatment. Materials & methods: Ex vivo expanded V gamma 9V delta 2 T cells were electroporated with anti-CD123 CAR-encoding mRNA. The effector function and specificity of the modified V gamma 9V delta 2 T cells were examined by in vitro cytotoxicity, degranulation and cytokine release level. The in vivo function was analyzed using the xenograft KG1-luc model with NOD-SCID-gamma c-/- mice. Results: The modified V gamma 9V delta 2 T cells exhibited significantly improved effector activities against both AML cell lines and primary AML cells in vitro. In the xenograft mouse model, the modified V gamma 9V delta 2 cells displayed an enhanced tumor control potency. Conclusion: Anti-CD123 CAR-expressing V gamma 9V delta 2 T cells may serve as an alternative way to target AML.