Carcinoembryonic antigen-derived peptide presented by HLA-A*0201 (CEA/HLA-A*0201)

The CEA-derived peptide presented by HLA-A*0201 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for T-cell-based cancer immunotherapies. Carcinoembryonic antigen (CEA), also known as CEACAM5, is a cell-surface glycoprotein that is overexpressed in over 90% of colorectal cancers and various other solid tumors, while its expression in normal tissues is limited to the luminal surface of the gastrointestinal tract (Tsang et al., 1995). Intracellular processing of CEA results in the generation of immunogenic peptides, most notably the 9-amino acid CAP-1 peptide (YLSGANLNL), which is presented on the cell surface by the HLA-A*0201 allele (Zaremba et al., 1997). This pMHC complex allows for the precise targeting of malignant cells by engineered T-cell receptors (TCRs) or TCR-like antibodies, bypassing the need for surface protein expression if the intracellular protein is abundant. Current therapeutic approaches include TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines designed to elicit a robust cytotoxic T-lymphocyte response. However, clinical development has faced challenges such as on-target, off-tumor toxicity, specifically severe inflammatory colitis, due to the recognition of low-level CEA expression in normal intestinal epithelium (Parkhurst et al., 2011).

Other names

CAP-1/HLA-A*0201CEA peptide-HLA-A*0201 complexCEACAM5-derived peptide/HLA-A*0201CEA-A2 complexYLSGANLNL/HLA-A*0201

The mechanism of action involves the recognition of the peptide-MHC complex by specific T-cell receptors (TCRs), leading to the activation of cytotoxic T lymphocytes and the subsequent release of perforins and granzymes to induce apoptosis in target tumor cells.