Carcinoembryonic antigen peptide-HLA complex (CEA-pMHC)

Carcinoembryonic antigen (CEA), also known as CEACAM5, is a cell surface glycoprotein primarily involved in cell adhesion and is a well-characterized tumor-associated antigen (UniProt: P06731). While CEA is expressed at low levels in normal mucosal cells, it is highly overexpressed in approximately 95% of colorectal, gastric, and pancreatic cancers (PubMed: 15649951). The target "CEA presented via MHC" refers to the peptide-MHC (pMHC) complex formed when intracellularly processed CEA fragments, such as the immunodominant CAP-1 peptide (YLSGANLNL), are presented on the cell surface by Major Histocompatibility Complex Class I molecules, typically HLA-A*02:01 (PubMed: 9151698). This complex is specifically recognized by T-cell receptors (TCRs), making it a critical target for TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers like IMC-C103C (Immunocore). By targeting the pMHC complex rather than the surface protein alone, these therapies can utilize the high sensitivity of the T-cell immune system to eliminate malignant cells that present CEA-derived antigens (PubMed: 28416541).

Other names

CEACAM5-MHC complexCEA-HLA-A*02:01 complexCEA peptide-MHCCarcinoembryonic antigen-related cell adhesion molecule 5 peptide-MHCCAP-1-HLA-A2 complex

T-cell receptor-mediated recognition of the specific CEA peptide presented by MHC Class I molecules, leading to T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and apoptosis of the target tumor cell.