使用新型双膦酸盐前药扩增的 CAR 修饰 Vγ9Vδ2 T 细胞用于同种异体过继免疫治疗

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity.

These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. V 9V 2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity.

Therefore, in this study, CAR-T cells were prepared from V 9V 2 T (CAR- T) cells which were expanded by using a novel prodrug PTA. CAR- T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR- T cells.

Our present results indicate that, while further optimization of CAR- T cells is necessary, the present results demonstrate that V 9V 2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.