DSG2-directed allogeneic CAR-T cells

DSG2-directed allogeneic CAR-T cells (also referred to as αDSG2 CAR-T cells) are an investigational, off-the-shelf cell-based immunotherapy developed by researchers at Thomas Jefferson University for the treatment of solid tumors. The therapy consists of healthy donor T cells engineered with a third-generation chimeric antigen receptor (CAR) specific for Desmoglein 2 (DSG2), a desmosomal cadherin protein universally overexpressed on the surface of cancerous epithelial cells. To enable universal application and mitigate immune rejection, the cells are modified using a cytosine base editor (CBE) to genetically disrupt the T-cell receptor (TCRαβ), β2-microglobulin (β2M), and RFX5, thereby eliminating MHC class I and II expression. Additionally, the cells are engineered to express HLA-E on their surface to protect against natural killer (NK) cell-mediated attack. Preclinical studies have demonstrated robust antitumor activity across multiple indications, including colorectal, pancreatic, lung, and breast cancers, while maintaining a favorable safety profile due to the junctional restriction of DSG2 in normal tissues.

Other names

αDSG2 CAR-T cellsDSG2 CAR-T cellsDSG-2 CAR-T cellsDSG 2 CAR-T cellsoff-the-shelf DSG2 CAR-T cells