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

The carcinoembryonic antigen (CEA)-derived peptide–MHC class I complex is a molecular assembly consisting of a processed peptide fragment from the CEACAM5 protein bound to a Major Histocompatibility Complex (MHC) class I molecule, typically HLA-A*02:01. This complex is a critical target in cancer immunotherapy because it serves as the specific ligand recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes. When presented on the surface of professional antigen-presenting cells like dendritic cells, the complex facilitates the priming and expansion of CEA-specific T cells, a process often exploited in dendritic cell-based vaccines and peptide vaccines (Tsang et al., 1995, Clin Cancer Res). In the context of the tumor microenvironment, the presence of this complex on malignant cells allows these primed T cells to identify and eliminate the tumor. Therapeutic interventions targeting this complex include TCR-engineered T-cell therapies and TCR-like monoclonal antibodies, which aim to overcome the immune tolerance often associated with CEA-expressing cancers such as colorectal, pancreatic, and lung adenocarcinomas (Parkhurst et al., 2011, Mol Ther). However, safety concerns remain regarding on-target off-tumor effects, as CEA is also expressed at lower levels in normal intestinal epithelium, which has led to clinical observations of severe inflammatory colitis in some T-cell therapy trials (Morse et al., 1999, Clin Cancer Res).

Other names

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

Induction of antigen-specific cytotoxic T-lymphocyte response through T-cell receptor recognition of the peptide-MHC complex presented on dendritic cells or tumor cells.