DSG2 靶向 CAR-T 细胞安全且广谱清除实体瘤

CAR-T cell therapies are curative for advanced hematologic cancers, however that potential has yet to be realized in epithelia-derived solid tumors reflecting the limited portfolio of cancer-restricted, cell-surface targets. Desmoglein 2 (DSG2) is a desmosomal cadherin universally overexpressed on the surface of transformed epithelial cells, with normal protein expression believed to be junctionally-restricted between adjacent cells, creating a "window of opportunity" to eliminate solid tumors without toxicity.

Here, we generated DSG2-directed CAR-T cells ( DSG2) that universally recognize and lyse assorted solid tumor cell lines in vitro and eliminated patient-derived and cell-derived colon, pancreatic, lung, prostate, breast, and liver tumors in vivo. Transgenic mice expressing human DSG2 experienced no toxicity following DSG2 CAR-T cell administration. These studies reveal safe and robust antitumor activity of DSG2 CAR-T cells and introduce a new class of junctionally-restricted antigens that can be safely and effectively targeted across solid tumor types.