Carcinoembryonic antigen-related cell adhesion molecule 5-derived peptide presented by Human Leukocyte Antigen A*02:01 (CEA/HLA-A*02:01)

The CEACAM5-derived epitope CEA as presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for advanced cancer immunotherapies (Source: PubMed PMID: 32814748). CEACAM5, also known as Carcinoembryonic Antigen (CEA), is a cell surface glycoprotein that is highly overexpressed in various solid tumors, particularly colorectal, pancreatic, and gastric cancers (Source: UniProt P06731). The specific epitope, typically the 9-amino acid CAP-1 peptide (YLSGANLNL), is generated through intracellular proteasomal processing and subsequently presented on the cell surface by the HLA-A*02:01 molecule (Source: PubMed PMID: 9047241). This pMHC complex allows the immune system, specifically CD8+ T-cells, to identify and eliminate malignant cells that express the CEA protein. Therapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers, such as IMC-C103C, which are designed to bind the pMHC with high affinity and specificity (Source: Immunocore). Because CEA is also expressed at lower levels in normal intestinal tissues, a primary therapeutic challenge is managing on-target off-tumor toxicity, which can manifest as gastrointestinal inflammation (Source: PubMed PMID: 34155013). Additionally, as with many T-cell engaging therapies, there is a risk of cytokine release syndrome (CRS) during treatment.

Other names

CEA-HLA-A2 complexCAP-1/HLA-A*02:01CEACAM5 epitope-MHC complexCEA peptide-HLA-A*02:01 complexYLSGANLNL-HLA-A*02:01

T-cell redirection and activation via T-cell receptor (TCR) or TCR-mimetic binding to the peptide-MHC complex, leading to granzyme/perforin-mediated lysis of tumor cells.