Human papillomavirus E6 and E7 oncoprotein-derived peptides presented on major histocompatibility complex molecules (HPV E6/E7 pMHC)

Human papillomavirus (HPV) E6 and E7 oncoprotein-derived peptides presented on major histocompatibility complex (MHC) molecules are primary targets for immunotherapy in HPV-driven malignancies. In these cancers, the E6 and E7 viral proteins are constitutively expressed and play a central role in oncogenesis by inhibiting the p53 and pRb tumor suppressor pathways, respectively (Source: NIH, National Cancer Institute). These proteins are processed intracellularly and presented as short peptide fragments on the cell surface via MHC molecules, making them visible to the immune system as non-self antigens. Because these antigens are exclusively expressed in HPV-infected and cancerous cells, they provide a high degree of tumor specificity for therapeutic interventions such as TCR-engineered T-cells (TCR-T) and therapeutic vaccines (Source: PubMed, PMID: 33067318). Current clinical strategies, such as those utilizing KITE-439 or ISA101, aim to stimulate or provide a robust T-cell response against these specific pMHC complexes to induce tumor regression. However, the effectiveness of these therapies can be limited by the requirement for specific HLA alleles, such as HLA-A*02:01, and the potential for tumors to evade detection through the downregulation of MHC expression (Source: Nature Reviews Cancer, doi:10.1038/nrc.2017.118).

Other names

HPV16 E6/E7 peptidesHPV18 E6/E7 peptidesHPV-derived T-cell epitopesHPV E6/E7-HLA complexesHPV-associated tumor antigens

The mechanism involves the recognition of specific viral peptide sequences (epitopes) bound to the groove of MHC molecules by the T-cell receptor (TCR) of CD8+ or CD4+ T-cells. This interaction, often enhanced by therapeutic vaccines or engineered TCR-T cells, triggers the release of perforins and granzymes, leading to the apoptosis of HPV-infected or transformed cells (Source: PubMed, PMID: 29038255).