Carcinoembryonic antigen-derived peptide-MHC complex (CEA-pMHC) (CEA-pMHC)

Carcinoembryonic antigen (CEA), also known as CEACAM5, is a cell surface glycoprotein that is highly expressed in various human carcinomas, particularly colorectal, gastric, and pancreatic cancers, while showing limited expression in normal adult tissues [UniProt P06731]. CEA-derived epitopes, such as the highly immunogenic CAP-1 peptide (YLSGANLNL), are generated through intracellular proteasomal processing and subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 [PubMed: 15649959]. These peptide-MHC (pMHC) complexes serve as specific targets for advanced immunotherapies, including T-cell receptor (TCR) engineered T cells and bispecific T-cell engagers (BiTEs) or ImmTACs [Immunocore]. Unlike traditional monoclonal antibodies that target the surface protein, pMHC-targeting agents can recognize antigens derived from intracellular proteins, offering a more refined approach to tumor specificity. Therapeutic strategies targeting these epitopes aim to induce potent T-cell mediated lysis of tumor cells while minimizing damage to normal tissues that express low levels of the parent CEA protein. However, challenges remain regarding "on-target, off-tumor" toxicities, such as inflammatory responses in the gastrointestinal tract where CEA is physiologically present [PubMed: 21248300].

Other names

CEA-derived epitopes presented by MHCCAP-1/HLA-A*02:01 complexCEACAM5 peptide-MHCCarcinoembryonic antigen-derived epitopes

T-cell redirection and activation leading to targeted lysis of cells presenting CEA-derived peptides on MHC class I.