用 Vγ9Vδ2 CAR-T 细胞克服 CAR-T 治疗中的抗原丢失

V 9V 2 T-cells demonstrate potent antitumor activity in vitro but, despite successful safety studies, the clinical benefit of V 9V 2 in adoptive cell therapy has been limited. One approach to enhance the therapeutic potential of V 9V 2 T-cells while maintaining their safety profile is genetic engineering to express a chimeric antigen receptor (CAR). V 9V 2 CAR T-cells retain the ability to target tumor cells even after target antigen loss, a major cause of CAR treatment relapse.

V 9V 2 T-cells were expanded from peripheral blood mononuclear cells in the presence of high levels of interleukin 2 (IL-2) or IL-2 in combination with IL-15. Cells were then virally transduced with a CD19-directed CAR and underwent antigen-specific stimulation to enrich CAR-expressing cells.

V 9V 2 CAR T-cells showed similar cytotoxic activity to conventional -CAR T-cells against CD19-positive tumor cells. They demonstrated superior responses against CD19-negative tumor cells, however, particularly when IL-15 was included during expansion. This enhanced function was further confirmed in co-culture assays with mixed CD19-positive and CD19-negative tumor populations, simulating antigen loss.

V 9V 2 CAR T-cell therapy presents a promising strategy for B-cell malignancies, offering sustained antitumor activity even after antigen loss. This approach may help overcome a major limitation of conventional CAR T-cell therapy, potentially improving clinical outcomes.