1064 Desmoglein 2 is a safe and universal CAR-T cell therapy target in solid cancers

Adoptive therapies employing T cells engineered to express a chimeric antigen receptor (CAR) have produced curative outcomes in refractory, progressive hematologic cancers, yet the same potential has be fully realized epithelial-derived solid tumors. A major obstacle is limited portfolio of cancer-restricted, cell-surface targets without expression normal tissues. Desmoglein 2 (DSG2) desmosomal cadherin protein universally over-expressed on surface transformed cells, with sequestered between cell-to-cell junctions. We hypothesize that this sequestration creates “window-of-opportunity” eliminate tumor malignancies off-tumor toxicity. In context, we generated DSG2-directed CAR-T recognize and lyse cell lines vitro. eliminated various cancer xenografts vivo, including colon, pancreatic, lung, squamous carcinoma. Tumor re-challenge previously treated mice indicated persistent vivo populations capable rejecting tumors, but not DSG2-deleted (CRISPR/Cas9) Moreover, syngeneic transfer species cross-reactive no overt toxicity targeting murine DSG2, ubiquitously expressed among Likewise, observed ex recognition lysis keratinocytes isolated from expressing human DSG2 transgene when cultured cells. Human transgenic receiving signs toxicity, indicating an ability detect accessible 2D monolayer, 3D tissue environment. These studies reveal robust antitumor activity introduce new class junctionally-restricted antigens can safely effectively targeted across types, skin cancers.