Carcinoembryonic antigen-derived peptide-HLA class I complex (CEA-HLA-I)

The Carcinoembryonic antigen (CEA)-derived peptide presented by HLA class I molecules is a specific tumor-associated antigen complex (UniProt P06731). CEA, or CEACAM5, is a cell surface glycoprotein primarily involved in cell adhesion and is highly overexpressed in various epithelial malignancies, particularly colorectal cancer (PubMed 7595737). In cancer cells, CEA is processed into short peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*02:01. The most well-characterized of these peptides is CAP-1 (YLSGANLNL), which serves as a target for the cellular immune response (PubMed 12149254). This peptide-MHC complex is a focal point for advanced immunotherapies, including TCR-engineered T-cells and bispecific T-cell engagers like IMC-C103C (ImmunoCore). These therapies are designed to bypass natural immune tolerance by providing high-affinity recognition of the complex. Clinical applications primarily target colorectal, gastric, and pancreatic cancers where CEA expression is prevalent (PubMed 33868301). A significant challenge in targeting this complex is the potential for on-target, off-tumor toxicity because CEA is expressed at low levels in normal intestinal and lung tissues (PubMed 25103341).

Other names

CEA-HLA-A2 complexCAP-1-HLA-A*02:01 complexCEACAM5 peptide-MHCCEA-derived peptide-MHC class I complex

T-cell redirection and activation via T-cell receptor (TCR) recognition of the peptide-MHC complex