Carbonic anhydrase 9-derived peptide presented on MHC class I (CA9-pMHC)

Carbonic anhydrase 9 (CA9)-derived peptide presented on MHC class I is a tumor-associated antigen complex used as a target for T-cell-based immunotherapies. CA9 is a membrane-associated enzyme that regulates intracellular pH and is highly upregulated in response to hypoxia, particularly in clear cell renal cell carcinoma (ccRCC) due to the loss of the von Hippel-Lindau (VHL) gene (UniProt: Q16790). The target consists of specific CA9-derived epitopes, such as the HLA-A*02:01-restricted peptide LLALVFGLL, which are processed and presented on the cell surface by MHC class I molecules (PubMed: 15501977). This presentation allows the immune system to distinguish malignant cells from healthy tissue, as CA9 expression is minimal in most normal organs except for the gastrointestinal tract and gallbladder (PubMed: 22964334). Therapeutic interventions targeting this complex include peptide-based vaccines like IMA901 and adoptive cell therapies using T-cells engineered with CA9-specific T-cell receptors (TCRs) (PubMed: 25113973). By binding specifically to the peptide-MHC interface, these therapies induce targeted lysis of tumor cells while attempting to minimize off-tumor effects. However, potential safety concerns include low-level expression in normal bile duct epithelium, which may lead to on-target off-tumor toxicity.

Other names

CAIX-pMHCG250 peptide-HLA complexHLA-A*02:01-restricted CA9 peptideCarbonic anhydrase 9 peptide-MHC

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte activation leading to tumor cell lysis.