Human papillomavirus type 16 E6 and E7 peptides presented on Human Leukocyte Antigen A*02 (HPV16 E6/E7-HLA-A*02)

The target consists of specific peptide fragments derived from the E6 and E7 oncoproteins of Human Papillomavirus type 16 (HPV16), which are processed and presented on the cell surface by the Human Leukocyte Antigen A*02 (HLA-A*02) MHC class I molecule [UniProt P03126, P03129]. HPV16 is a high-risk virus and the primary causative agent of various malignancies, including cervical, oropharyngeal, and anal cancers [NCI]. In these cancers, the E6 and E7 viral proteins are constitutively expressed and are essential for the induction and maintenance of the malignant phenotype by degrading tumor suppressors p53 and pRb, respectively [PubMed PMID: 32015143]. Because these viral proteins are absent in healthy human tissues, the E6/E7-HLA-A*02 complex serves as a highly specific tumor-associated antigen for immunotherapy. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies, T-cell engagers, and therapeutic vaccines designed to elicit a robust CD8+ T-cell response [ClinicalTrials.gov NCT04634760, NCT02858310]. Clinical development focuses on patients who are HLA-A*02 positive and have HPV16-positive tumors, aiming to induce targeted apoptosis of cancer cells while sparing normal tissue.

Other names

HPV16 E6/E7-HLA-A2HPV16 E6/E7-MHC complexHPV16 E6/E7-HLA-A*02:01HPV16 E6/E7-HLA complexHPV16 E6/E7-peptide-MHC

Therapeutic agents targeting this complex function by either delivering the viral antigens to stimulate an endogenous CD8+ T-cell response (vaccines) or by utilizing engineered T-cell receptors (TCR-T) and bispecific molecules that directly bind the peptide-HLA complex to trigger T-cell mediated cytotoxicity against HPV-infected malignant cells [PubMed PMID: 32015143, ClinicalTrials.gov NCT04634760].