(W1001) Allogeneic iPS cell-derived gamma-delta T cells demonstrate cytotoxicity against patient-derived colorectal cancer tissues via local and intravenous administration
Abstract: Objective Various immunotherapies are being developed to treat malignant tumors. γδT cells, which constitute 3–5% of peripheral blood lymphocytes, have attracted attention for their potent cytotoxic activity and ability to target a broad range of tumors in an MHC-unrestricted manner. We successfully derived γδT cells from induced pluripotent stem cells (iPS cells) and demonstrated their cytotoxic effects against a colorectal cancer cell line in vitro. However, cancer cell lines often lack key tumor characteristics, such as heterogeneity and drug sensitivity. In contrast, patient-derived colorectal cancer organoids (PDCOs) retain many features of the original tumor tissue. This study aimed to evaluate the cytotoxicity of allogeneic iγδT cells against colorectal cancer cell lines and PDCOs in both in vitro and in vivo models. Methods We assessed the cytotoxicity of iγδT cells against the colorectal cancer cell line SW480 and PDCOs in vitro. Next, the cell line and organoids were transplanted subcutaneously into immunodeficient mice. iγδT cells were administered either locally at transplantation or intravenously after confirming tumor formation through IVIS luminescence imaging. Tumor growth in treated groups was compared with untreated groups to evaluate the in vivo cytotoxicity of iγδT cells. Results In vitro, allogeneic iγδT cells demonstrated over 90% cytotoxicity against the SW480 cell line and 70–90% against the two PDCO lines. In vivo, local administration of iγδT cells suppressed tumor growth by over 80% in mice transplanted with the cell line and by 90–100% in those transplanted with PDCOs. Intravenous administration of iγδT cells to PDCO-transplanted mice resulted in over 70% tumor cytotoxicity. Similarly, intravenous administration after confirming tumor formation achieved comparable cytotoxicity exceeding 70%. Conclusion Allogeneic iγδT cells showed significant cytotoxicity against patient-derived colorectal cancer tissues in vitro and in vivo. Their efficacy was observed with both local and intravenous administration. These findings suggest that allogeneic iγδT cells hold promise as a novel immunotherapy for colorectal cancer.
