Vgd1 and Vgd3 T cells infiltrate non-small/small cell lung cancer, high-grade serous ovarian carcinoma and can be expanded from human umbilical cord blood for allogeneic CAR-T cell therapies 4461

Abstract Description gd T cells recognize and kill tumor cells in a MHC-unrestricted manner with potential use for anti-tumor allogeneic CAR T cell therapies. gd TILs phenotypes in human solid tumors remain poorly understood. In order to study this, we first, characterized the repertoire of gd-chains expressed by gd TILs from FACS-sorted dissociated tumors of non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and high-grade serous ovarian carcinoma. Second, we developed a CAR T cell platform using human umbilical cord blood (UCB)-derived gd T cells. Third, by scBCR-seq of CD138+ plasma cells from ICI non-responder patients, we identified scFv sequences specific for the surface protein Vimentin expressed in tumor and tumor-promoting cells. Our data showed that d1 and d3 TILs are abundant in solid tumors, expressing wide Vg-chain repertoire. Importantly, single cell transcriptome analyses showed distinctive clusters of stem-like cells expressing TCF7, IL7R and CD27; plus effector T cells expressing high levels of granzymes, IFNG, perforin and NK receptors. Moreover, we expanded clinically relevant amounts of Vd1/d3 T cells from UCB which also showed a wide usage of Vg-chains and expression of IFNG, PRF1 and GZMB; cell stemness markers CD27, TCF7 and NK receptors. Finally, allogeneic gd CAR T cells targeting cell surface Vimentin showed high cytotoxic activity of tumor cells, without expression on vital issues, providing a rationale for a new platform to treat human cancers. Funding Sources This study was supported by The National Institute of Health/National Cancer Institute grant numbers R01CA124515, R01CA278907, R21CA276205, and a CLIP Award from the Cancer Research Institute, to J.R.C.-G. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)