T cell receptor recognizing Carcinoembryonic antigen-derived peptide CAP1-6D–HLA-A*02:01 complex (TCR-CAP1-6D-HLA-A2)

The T cell receptor (TCR) recognizing the CAP1-6D–HLA-A2 complex is a specialized immune receptor engineered to target the Carcinoembryonic Antigen (CEA), a well-characterized tumor-associated antigen (Zaremba et al., 1997). CEA is highly expressed in various epithelial malignancies, including colorectal, gastric, and pancreatic cancers, while its expression in normal adult tissues is primarily limited to the gastrointestinal tract. The CAP1-6D peptide (YLSGADLNL) is an altered peptide ligand of the native CEA-derived CAP1 epitope, modified with an asparagine-to-aspartic acid substitution at position 6 to enhance its binding affinity for the HLA-A*02:01 molecule (Roszkowski et al., 2003). This increased affinity improves the stability of the peptide-MHC complex, thereby facilitating more robust recognition and activation of TCR-engineered T cells. Upon binding to the CAP1-6D–HLA-A2 complex on the surface of tumor cells, the TCR initiates a signaling cascade that leads to the release of cytotoxic granules and pro-inflammatory cytokines, resulting in tumor cell lysis. This target is a focal point for adoptive cell transfer therapies, specifically TCR-T cell products, aimed at treating advanced CEA-expressing adenocarcinomas. However, clinical development must carefully manage on-target, off-tumor toxicities, such as severe colitis, which can occur due to the presence of CEA in normal colonic mucosa (Parkhurst et al., 2011).

Other names

CEA-specific T-cell receptorCAP1-6D-specific TCRTCR targeting CEA/HLA-A2Carcinoembryonic antigen-specific TCRTCR recognizing YLSGADLNL-HLA-A2

The TCR specifically recognizes the CAP1-6D peptide presented by HLA-A*02:01 on the surface of tumor cells, leading to T-cell activation, secretion of cytotoxic cytokines (e.g., IFN-gamma, TNF-alpha), and direct granzyme/perforin-mediated lysis of the target cell.