Carcinoembryonic antigen-derived peptide–HLA-A*02:01 complex (CEA-pMHC) (CEA-pMHC)

The Carcinoembryonic antigen (CEA)-derived peptide–MHC class I complex is a molecular target consisting of a specific peptide fragment of the CEACAM5 protein bound to a Major Histocompatibility Complex (MHC) molecule, most commonly HLA-A*02:01 (Tsang et al., 1995, PMID 7538208). CEA is a cell-surface glycoprotein that is highly overexpressed in various epithelial malignancies, including colorectal, gastric, and pancreatic cancers (Gold & Freedman, 1965, PMID 14331143). In healthy adults, CEA expression is primarily restricted to the luminal surface of the gastrointestinal epithelium, making it a classic tumor-associated antigen. This peptide-MHC (pMHC) complex is specifically recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which triggers a targeted immune response against the cancer cell. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and TCR-like antibodies, which aim to exploit the intracellular proteome of the tumor (Parkhurst et al., 2011, PMID 21220592). A significant clinical challenge associated with this target is on-target off-tumor toxicity, as T cells may attack normal tissues expressing low levels of CEA. For instance, clinical trials using high-affinity CEA-specific TCR-T cells have reported severe inflammatory colitis in treated patients (Parkhurst et al., 2011). Despite these challenges, the CEA-pMHC complex remains a high-priority target for developing more refined and safer immunotherapies for solid tumors.

Other names

CEA-derived peptide–MHC class I complex recognized by CEA-specific T-cell receptorCEACAM5-peptide-MHC complexCAP-1-HLA-A*02:01 complexCEA-HLA-A2 complexCarcinoembryonic antigen-derived peptide–MHC class I complex

T-cell receptor-mediated recognition of the peptide-MHC complex leading to directed T-cell cytotoxicity and cytokine release.