Carcinoembryonic antigen CAP-1 peptide epitope presented by HLA-A*02:01 (CEA CAP-1/HLA-A2)

The Carcinoembryonic antigen (CEA) CAP-1 peptide epitope is a specific nine-amino acid sequence (YLSGANLNL) derived from the CEACAM5 protein, which is processed and presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule [PMID: 7623877]. CEA is a glycosylphosphatidylinositol (GPI)-linked oncofetal glycoprotein that is highly overexpressed in over 90% of colorectal cancers, as well as many pancreatic, gastric, and lung adenocarcinomas, making it a prime target for cancer immunotherapy [PMID: 12183334]. The CAP-1/HLA-A2 complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the tumor cells [PMID: 9314481]. Therapeutic interventions targeting this epitope include various vaccine platforms, such as the ALVAC-CEA viral vector and PANVAC, as well as adoptive cell therapies using TCR-engineered T cells [PMID: 15897564]. A modified heteroclitic analog, CAP-1-6D (YLSGADLNL), has been developed to enhance the binding affinity to HLA-A2 and increase the immunogenicity of the epitope for clinical applications [PMID: 9314481]. Clinical trials have demonstrated that targeting this epitope can induce measurable T-cell responses, although therapeutic efficacy often requires overcoming the immunosuppressive tumor microenvironment [PMID: 18483463]. Safety considerations include potential on-target off-tumor effects due to low-level CEA expression in normal gastrointestinal tissues [PMID: 15897564].

Other names

CEA(571-579)YLSGANLNLCAP-1CEA CAP-1HLA-A*02:01-restricted CEA epitopeCarcinoembryonic antigen-related cell adhesion molecule 5 (571-579) epitope

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) response leading to tumor cell lysis