Cyclooxygenase-2 peptide–Major Histocompatibility Complex (COX-2 pMHC)

The Cyclooxygenase-2 (COX-2) peptide–Major Histocompatibility Complex (MHC) is a molecular target used in cancer immunotherapy, consisting of a processed peptide fragment of the COX-2 enzyme bound to an MHC molecule, typically HLA-A*0201 (PubMed: 11160381). While COX-2 is primarily known for its role in prostaglandin synthesis and inflammation, it is significantly overexpressed in a wide range of solid tumors, including colorectal, breast, and lung cancers, as well as gliomas (PubMed: 15050911). This overexpression leads to the presentation of COX-2-derived peptides on the cell surface, making them visible to the adaptive immune system. Therapeutic interventions, such as peptide vaccines and T-cell receptor (TCR)-engineered T-cell therapies, are designed to recognize this specific pMHC complex to induce a cytotoxic T-lymphocyte response against tumor cells (PubMed: 24651531). However, because COX-2 is also expressed at lower levels in certain healthy tissues like the kidneys and gastric mucosa, targeting this complex carries a risk of on-target, off-tumor toxicity (PubMed: 10661151). Consequently, patient selection often requires screening for both high COX-2 expression and the appropriate HLA genotype.

Other names

PTGS2 peptide-HLA complexCOX-2 peptide-HLA-A*0201 complexCOX-2(282-290)/HLA-A2HLA-A2/COX-2 complex

Recognition by specific T-cell receptors (TCRs) on cytotoxic T lymphocytes, leading to the release of perforins and granzymes that induce apoptosis in the target cell.