CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy

作者：Yizheng Wang, Linan Wang, Naohiro Seo, Satoshi Okumura, Tae Hayashi, Yasushi Akahori, Hiroshi Fujiwara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Yoshimasa Tanaka, Takuma Kato, Hiroshi Shiku · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms241310873 · 被引用次数：17 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Viral Infectious Diseases and Gene Expression in Insects

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ 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. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ 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-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.