HLA-A*02:01-restricted Carcinoembryonic Antigen peptide CAP-1 complex (HLA-A2/CEA CAP-1)

The HLA-A*02:01-restricted Carcinoembryonic Antigen (CEA) CAP-1 peptide-MHC complex is a specific molecular target formed when the intracellularly processed CAP-1 peptide (sequence: YLSGANLNL) from the CEACAM5 protein is loaded onto HLA-A*02:01 molecules and presented on the cell surface (Tsang et al., 1995). This complex is primarily found on the surface of various adenocarcinomas, including colorectal, pancreatic, and lung cancers, where CEA is overexpressed. Unlike traditional antibodies that target the surface protein, therapies directed at this pMHC complex, such as TCR-engineered T cells, allow for the recognition of intracellularly derived antigens. The CAP-1 epitope is highly immunogenic and has been the focus of numerous clinical trials involving peptide vaccines and adoptive cell therapies (Zaremba et al., 1997). However, therapeutic application must account for the low-level expression of CEA in normal gastrointestinal tissues to avoid off-tumor toxicity. Clinical studies have demonstrated that targeting this complex can induce significant tumor regression but may also lead to severe adverse events like inflammatory colitis (Parkhurst et al., 2011).

Other names

CEA CAP-1/HLA-A*02:01 complexCEACAM5 peptide-MHC complexYLSGANLNL-HLA-A*02:01 complexCEA-specific TCR targetCAP-1 pMHC

The target complex is recognized by the T-cell receptor (TCR) of engineered T cells or vaccine-induced endogenous T cells, triggering an immunological synapse that leads to the release of cytotoxic granules (perforin and granzymes) and the subsequent lysis of the CEA-presenting tumor cell (Parkhurst et al., 2011; Tsang et al., 1995).