Carcinoembryonic antigen-derived peptide-MHC complex (CEA-pMHC)

The Carcinoembryonic antigen-derived peptide-MHC complex (CEA-pMHC) is a specialized therapeutic target consisting of short peptide fragments derived from the Carcinoembryonic Antigen (CEA/CEACAM5) protein presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (UniProt P06731; PubMed: 9151699). CEA is a cell-surface glycoprotein that is highly overexpressed in a variety of solid tumors, including colorectal, pancreatic, and non-small cell lung cancers, while its expression in healthy adult tissue is largely restricted to the gastrointestinal epithelium (PubMed: 21220592). The presentation of CEA-derived peptides, such as the immunodominant CAP-1 (YLSGANLNL) epitope, allows the immune system to recognize and eliminate malignant cells through T-cell receptor (TCR) engagement (PubMed: 9151699). Modern therapeutic interventions targeting this complex include TCR-engineered T-cell therapies (TCR-T) and bispecific T-cell engagers like ImmTACs (e.g., IMC-C103C), which bypass natural immune tolerance to trigger potent T-cell-mediated lysis of tumor cells (NCT03970382). However, the clinical application of these therapies is challenged by potential on-target off-tumor toxicity due to low-level CEA expression in normal tissues, necessitating precise patient selection based on HLA genotype and tumor antigen density (PubMed: 21220592).

Other names

CEA-HLA complexCEA peptide-HLA-A*02:01CAP-1/HLA-A2 complexCarcinoembryonic antigen-related cell adhesion molecule 5 peptide-MHCCEACAM5-pMHC

T-cell redirection and activation leading to lysis of CEA-expressing tumor cells.