Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) peptide-MHC complex (CEA-6D/MHC)

Carcinoembryonic antigen (CEA), also known as CEACAM5, is a cell surface glycoprotein that is highly expressed in various adenocarcinomas, including colorectal, pancreatic, and non-small cell lung cancers (UniProt P06731). The CEA-6D peptide (YLSGADLNL) is a synthetic agonist of the naturally occurring CAP-1 epitope, specifically modified at the sixth position to enhance its binding affinity to the HLA-A*02:01 MHC molecule and improve T-cell receptor (TCR) recognition (Zaremba et al., 1997, Cancer Research). When presented on the surface of tumor cells by MHC molecules, this complex serves as a target for cytotoxic T lymphocytes (CTLs), making it a focal point for cancer vaccines and TCR-engineered T-cell therapies. Drugs such as the PANVAC vaccine platform utilize this epitope to stimulate an anti-tumor immune response in patients with advanced gastrointestinal malignancies (Fong et al., 2001, Journal of Immunology). However, the therapeutic use of this target is complicated by the expression of CEA in normal intestinal tissues, which can lead to on-target, off-tumor toxicities such as severe colitis (Parkhurst et al., 2011, Molecular Therapy). Consequently, patient selection often requires screening for both HLA-A*02:01 positivity and high tumor CEA expression to maximize efficacy and manage safety risks.

Other names

CAP1-6DYLSGADLNLCEA peptide 6DHLA-A*02:01-restricted CEA epitopeCarcinoembryonic antigen-derived peptide 6D

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T lymphocyte (CTL) activation and tumor cell lysis.