Carcinoembryonic antigen-related cell adhesion molecule 5 peptide-HLA class I complex (CEA peptide-HLA complex)

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), or CEA, is a cell surface glycoprotein primarily associated with cell adhesion and is highly expressed in various epithelial cancers, particularly colorectal carcinoma (UniProt: P06731). The target specifically refers to processed CEA peptides, such as the immunodominant CAP-1 (YLSGANLNL), presented by HLA class I molecules (most commonly HLA-A*0201) on the surface of antigen-presenting cells like dendritic cells (Tsang et al., Clin Cancer Res, 1995). This presentation is a prerequisite for the activation of CD8+ cytotoxic T lymphocytes (CTLs) which can then recognize and lyse CEA-expressing tumor cells. Therapeutic interventions targeting this complex include dendritic cell vaccines pulsed with CEA peptides or transfected with CEA mRNA, as well as recombinant viral vaccines like PANVAC (Gulley et al., Clin Cancer Res, 2008). Additionally, adoptive T-cell therapies using T-cell receptors (TCRs) engineered to recognize the CEA peptide-HLA complex are under clinical investigation (Parkhurst et al., Mol Ther, 2011). The primary challenge with this target is the potential for on-target, off-tumor toxicity due to low-level CEA expression in normal intestinal tissues, which has historically led to severe adverse events in high-affinity TCR-T trials.

Other names

CEA-derived peptidesCAP-1 peptideCEACAM5-derived peptidesHLA-A*0201/CEA complexCEA-pMHCCarcinoembryonic antigen-derived peptides

Induction of antigen-specific cytotoxic T lymphocyte (CTL) responses through the presentation of tumor-associated peptides by HLA class I molecules to T-cell receptors (TCRs).