Chimeric antigen receptor (CAR) αβ T cell adoptive immunotherapy has shown great promise for improving
cancer treatment. However, there are several hurdles to overcome for the wide clinical application of CAR-αβ T cells
therapy, including side effects and a limited T cells source from
cancer patients. Therefore, we sought to identify an alternative T cell subset that could avoid these limitations and improve the effectiveness of CAR-T
immunotherapy. γδ T cells are a minor subset of T cells, which share the characteristic of innate immune cells and adaptive immune cells. Vγ9Vδ2 T cells are a predominant γδ T subset in the circulating peripheral blood. In this study, we investigated the
antigen-specific antitumor activity of CAR-Vγ9Vδ2 T cells targeting MUC1-Tn
antigen. Vγ9Vδ2 T cells were expanded from peripheral blood mononuclear cells of healthy volunteers with
zoledronic acid and
interleukin-2. CAR-Vγ9Vδ2 T cells were generated by transfection of lentivirus encoding MUC1-Tn CAR. Cytotoxicity assays with various
cancer cell lines revealed that CAR-Vγ9Vδ2 T cells could effectively lyse
tumor cells in an
antigen-specific manner, with similar or stronger effects than CAR-αβ T cells. However, CAR-Vγ9Vδ2 T cells had shorter persistence, which could be improved with the addition of
IL-2 to maintain the function of CAR-Vγ9Vδ2 T cells with consecutive stimulation of
tumor cells. Using a xenograft mouse model, we further showed that CAR-Vγ9Vδ2 T cells more effectively suppressed
tumor growth in vivo than Vγ9Vδ2 T cells. Therefore, MUC1-Tn CAR-modified Vγ9Vδ2 T cells may represent a novel, promising ready-to-use product for
cancer allogeneic
immunotherapy.