Carcinoembryonic antigen-derived peptide–Major Histocompatibility Complex class I complex (CEA-peptide-MHC-I complex)

The Carcinoembryonic antigen-derived peptide–Major Histocompatibility Complex class I complex (CEA-peptide-MHC-I) is a molecular target formed when intracellularly processed fragments of the CEACAM5 protein are presented on the cell surface by MHC class I molecules, most commonly HLA-A*02:01 [PubMed, 9151699]. CEA is an oncofetal glycoprotein that is highly expressed in various epithelial malignancies, including colorectal, gastric, and pancreatic cancers, while showing limited expression in normal adult tissues [UniProt, P06731]. The presentation of CEA-derived peptides, such as the immunodominant CAP-1 (YLSGANLNL), allows for the recognition of tumor cells by the cellular immune system [PubMed, 10438932]. This complex is a primary target for next-generation immunotherapies like T-cell receptor (TCR) engineered T cells and bispecific TCR-mimetic molecules, such as ImmTACs, which bypass the need for natural T-cell priming [Immunocore, 2023]. By targeting the pMHC complex, these therapies can achieve high specificity for malignant cells that process and present CEA, potentially recruiting a potent T-cell response against intracellularly derived antigens that are otherwise inaccessible to standard monoclonal antibodies [Journal of Hematology & Oncology, 2021].

Other names

CEACAM5-peptide-HLA complexCEA-HLA-A2 complexCAP-1-HLA-A*02:01 complexCEA-pMHCCarcinoembryonic antigen-peptide-HLA-A*02:01 complex

T-cell redirection and activation through the specific recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimetic molecules, resulting in cytotoxic granule release and tumor cell apoptosis.