Carcinoembryonic antigen-derived peptide–Major Histocompatibility Complex (CEA-pMHC)

CEA-derived peptide–MHC complexes are tumor-associated antigens formed when peptides from the Carcinoembryonic Antigen (CEA/CEACAM5) are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (Parkhurst et al., 2011, NIH). CEA is a well-known oncofetal glycoprotein highly expressed in various adenocarcinomas, including colorectal, pancreatic, and lung cancers, while its expression in normal adult tissues is limited primarily to the gastrointestinal epithelium (Morse et al., 1999, NIH). These pMHC complexes serve as specific targets for T-cell receptor (TCR)-based therapies, such as TCR-engineered T cells (TCR-T) and peptide-based vaccines, which aim to redirect the immune system to recognize and eliminate malignant cells (He et al., 2019, NIH). A prominent example is the CAP-1 peptide (YLSGANLNL) and its agonist variant CAP-1(6D), which have been extensively studied in clinical trials for their ability to induce specific cytotoxic T-lymphocyte responses (Weihrauch et al., 2005, NIH). However, therapeutic targeting of CEA-pMHC faces significant challenges, notably on-target off-tumor toxicity, as evidenced by severe inflammatory colitis in clinical trials due to low-level CEA expression in normal colonic mucosa (Parkhurst et al., 2011, NIH). Despite these challenges, the high specificity of TCR-pMHC interactions continues to make this an attractive target for next-generation immunotherapies designed to minimize off-tumor effects.

Other names

CEA peptide-HLA complexCEACAM5 peptide-MHCCEA/HLA-A*02:01 complexCAP-1/HLA-A2 complexCEA-derived peptide-HLA-A2 complexCAP-1(6D)/HLA-A2 complexIMIGVLVGV/HLA-A2 complex

T-cell redirection and TCR-mediated cytotoxicity against cells presenting CEA-derived peptides on MHC molecules, as well as induction of antigen-specific T-cell responses through vaccination.