CAR-Modified V gamma 9V delta 2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous alpha beta 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 gamma 9V delta 2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from V gamma 9V delta 2 T (CAR-gamma delta T) cells which were expanded by using a novel prodrug PTA. CAR-gamma delta 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-gamma delta T cells. Our present results indicate that, while further optimization of CAR-gamma delta T cells is necessary, the present results demonstrate that V gamma 9V delta 2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.

Automated summary

The benefits of CAR-T therapy for solid tumors have been limited so far due to disappointing clinical trial results and the time and cost intensive preparation of CAR-T cell products. However, using third-party donor derived CAR-T cell products could potentially overcome these challenges. Vγ9Vδ2 T cells, which have potent antitumor activity, could be a potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.