Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues.

Various immunotherapies have been developed to treat malignant tumors, and autologous CAR-T cell therapy is clinically used for certain malignancies. However, their efficacy against solid tumors is limited. γδT cells are recognized for their potent tumor cytotoxicity and MHC-unrestricted activity. We successfully induced γδT cells from iPS cells and demonstrated their cytotoxicity against colorectal cancer cell lines in vitro. However, cancer cell lines often lack critical tumor characteristics such as heterogeneity and drug sensitivity. In contrast, patient-derived cancer organoids retain many features of the patient's tumor tissues. This study evaluated the cytotoxicity of allogeneic iγδT cells against cell lines and organoids, in vitro and in vivo. iγδT cells showed 70%-90% cytotoxicity against cell lines and organoids in vitro. In vivo, local and intravenous administration of iγδT cells suppressed tumor growth by 70%-100%, highlighting their potential as a novel immunotherapy for colorectal cancer.