Carcinoembryonic antigen-derived HLA-A*0201-restricted epitope (CEA/HLA-A*0201)

The Carcinoembryonic antigen-derived HLA-A*0201-restricted epitope is a specific peptide fragment, most commonly the CAP-1 sequence (YLSGANLNL), derived from the CEACAM5 protein and presented by the MHC class I molecule HLA-A*0201 (PubMed: 7591252). CEA is a cell surface glycoprotein that is highly overexpressed in a variety of solid tumors, including colorectal, gastric, and pancreatic cancers, while showing limited expression in normal adult tissues (UniProt: P06731). This peptide-MHC complex serves as a critical target for T-cell-based immunotherapies, as it allows the immune system to distinguish malignant cells from healthy ones. Therapeutic strategies targeting this complex include the development of TCR-engineered T cells and bispecific T-cell engagers designed to bind the peptide-MHC complex with high specificity. One prominent example is IMC-C103C, an ImmTAC molecule that redirects T cells to kill CEA-positive tumor cells (ClinicalTrials.gov: NCT03510286). Because CEA is also expressed at lower levels in normal mucosal tissues, safety monitoring for gastrointestinal toxicities is a critical component of clinical development. The use of agonist peptides like CAP-1-6D has also been explored to enhance the immunogenicity of vaccines targeting this epitope (PubMed: 10438934). Overall, this epitope represents a validated target for precision oncology in HLA-A*02:01 positive patients with CEA-expressing malignancies.

Other names

CAP-1CEA(605-613)YLSGANLNLCEACAM5-derived HLA-A*02:01 epitopeCAP-1-6D

T-cell receptor (TCR) mediated recognition and cytotoxic T-lymphocyte activation