Carcinoembryonic antigen-related cell adhesion molecule 5 peptide–MHC class I complex (CEACAM5 pMHC)

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CEA, is a cell surface glycoprotein that is highly overexpressed in various epithelial malignancies, including colorectal, pancreatic, gastric, and non-small cell lung cancers. While the protein itself is a target for antibody-drug conjugates, its intracellularly processed peptides are presented on the cell surface by MHC class I molecules, most commonly HLA-A*02:01. These peptide-MHC (pMHC) complexes, such as those containing the IMIGVLVGV (CEA 691-699) epitope, serve as specific targets for T-cell receptor (TCR)-based immunotherapies. By targeting the pMHC complex rather than the whole protein, therapeutic agents like TCR-engineered T cells (TCR-T) and TCR-like antibodies can engage the immune system to recognize and eliminate tumor cells presenting these specific antigens. However, clinical application is limited by the potential for on-target off-tumor toxicity, as low levels of CEA expression in normal tissues like the colon and lungs can lead to severe adverse events such as autoimmune colitis and pneumonitis.

Other names

CEA peptide-MHC complexCEA pMHCCarcinoembryonic antigen peptide-HLA complexHLA-A*02:01/CEA complexCEACAM5 pMHC complex

T-cell redirection and T-cell receptor-mediated cytotoxicity