Carcinoembryonic antigen-derived peptide presented by MHC class I (CEA-peptide-MHC-I)

The Carcinoembryonic antigen (CEA)-derived peptide presented by MHC class I is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various cancer cells (PMID: 7538202). CEA, also known as CEACAM5, is a cell surface glycoprotein that is highly overexpressed in many solid tumors, particularly colorectal, pancreatic, and gastric carcinomas (UniProt: P06731). Intracellular processing of the CEA protein results in short peptide fragments, such as the immunodominant CAP-1 peptide (YLSGANLNL), which are loaded onto MHC class I molecules—typically HLA-A*02:01—and transported to the cell surface (PMID: 9047241). This complex serves as a highly specific target for immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific molecules like ImmTACs (e.g., IMC-C103C) (ClinicalTrials.gov: NCT03510286). By targeting the pMHC rather than the whole protein, these therapies can achieve high specificity for malignant cells. However, because CEA is also expressed at lower levels in normal mucosal tissues, therapeutic strategies must carefully manage the risk of on-target off-tumor toxicity (PMID: 21670471).

Other names

CEA/HLA-A*02:01 complexCAP-1/HLA-A2 complexCEACAM5 peptide-MHC complexCEA-derived peptide-HLA complexCarcinoembryonic antigen-related cell adhesion molecule 5 peptide-MHC complex

Redirection of T-cells to recognize and lyse tumor cells expressing the specific CEA peptide-MHC complex.