Carcinoembryonic antigen peptide 691–699 presented by HLA-A*0201 (CEA(691-699)/HLA-A*0201)

The CEA:691–699 peptide presented by HLA-A*0201, commonly known as CAP-1 (Carcinoembryonic Antigen Peptide-1), is a highly studied immunogenic epitope derived from the Carcinoembryonic Antigen (CEACAM5) (Tsang et al., 1995). This peptide-MHC complex serves as a critical target for cancer immunotherapies because CEACAM5 is significantly overexpressed in a wide range of solid tumors, including colorectal, gastric, and pancreatic adenocarcinomas (UniProt P06731). The complex is formed when the intracellularly processed CEA protein is loaded onto the HLA-A*0201 molecule, a common MHC class I allele, and presented on the cell surface for recognition by CD8+ T cells. Therapeutic interventions targeting this specific complex include bispecific T-cell engagers like IMC-C103C, which redirect T cells to kill CEA-positive tumor cells (ClinicalTrials.gov, NCT03515551). Additionally, various TCR-engineered T-cell therapies and peptide vaccines have been developed to exploit this target for precision oncology. A significant therapeutic challenge is the potential for on-target, off-tumor toxicity, as CEA is also expressed at lower levels in normal gastrointestinal epithelial tissues. Monitoring HLA-A*0201 status and CEACAM5 expression levels is essential for patient selection in clinical trials involving this target.

Other names

CAP-1Carcinoembryonic antigen peptide 1YLSGANLNL peptideCEACAM5(691-699)/HLA-A*0201CEA-derived peptide CAP-1

T-cell redirection and activation via T-cell receptor (TCR) recognition of the peptide-MHC complex, leading to tumor cell lysis.