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

Carcinoembryonic antigen (CEA), specifically the CEACAM5 protein, is a cell surface glycoprotein primarily involved in cell adhesion and is highly overexpressed in various epithelial malignancies, most notably colorectal cancer (UniProt P06731). The target "CEA – antigenic epitope presented via MHC to TCR" refers to specific intracellularly processed CEA peptide fragments, such as the CAP-1 (YLSGANLNL) epitope, which are displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01 (Tsang et al., 1995). This peptide-MHC (pMHC) complex is the fundamental unit recognized by T-cell receptors (TCRs), making it a critical target for advanced immunotherapies like TCR-engineered T-cell (TCR-T) therapies and TCR-mimetic bispecific molecules. Therapeutic approaches such as ImmTACs (e.g., IMC-C103C) bypass the need for surface protein expression by targeting the processed antigen presented on MHC (Immunocore, 2023). By focusing on the pMHC complex, these therapies can exploit the high density of CEA in tumor cells while potentially minimizing interactions with soluble CEA that often acts as a decoy for traditional antibodies. However, because CEA is also expressed at lower levels in normal intestinal epithelium, "on-target, off-tumor" toxicities, including severe colitis, remain a significant clinical challenge (Park et al., 2011). Monitoring HLA status and CEACAM5 expression levels is essential for patient selection in these precision medicine frameworks.

Other names

CEACAM5 peptide-HLA complexCEA-HLA-A*02:01CAP-1/HLA-A2 complexCarcinoembryonic antigen-related cell adhesion molecule 5 epitopeCD66e peptide-MHC

T-cell receptor (TCR) mediated recognition and activation of cytotoxic T lymphocytes (CTLs) against cells presenting CEA-derived peptides on MHC molecules.