Human papillomavirus type 18 E7 peptide–MHC class I complex (HPV-18 E7–MHC-I)

The Human papillomavirus type 18 (HPV-18) E7 peptide–MHC class I complex is a specialized molecular target formed when the E7 oncoprotein of HPV-18 is processed and presented on the surface of infected cells by Major Histocompatibility Complex (MHC) class I molecules (UniProt P06788). HPV-18 is the second most common high-risk HPV type associated with cervical cancer and other anogenital and oropharyngeal malignancies (PubMed: 30287581). The E7 protein is essential for oncogenesis as it binds and inactivates the retinoblastoma protein (pRb), driving the cell into the S-phase of the cell cycle (PubMed: 10482235). Because E7 is a foreign viral protein constitutively expressed in tumor cells but absent in healthy human tissue, its peptide-MHC complex represents an ideal near-neoantigen for immunotherapy. Current therapeutic approaches focus on T-cell receptor (TCR) engineered T-cell therapies, such as KITE-439, which are designed to recognize specific E7 peptides (e.g., E7 11-19) in the context of specific HLA alleles like HLA-A*02:01 (ClinicalTrials.gov: NCT04634149). These therapies aim to induce direct cytotoxic T-lymphocyte (CTL) mediated killing of the cancer cells. However, the efficacy of these treatments can be limited by tumor-induced MHC downregulation or the high degree of HLA polymorphism in the human population, necessitating patient screening for compatible HLA types.

Other names

HPV18 E7-HLA complexHPV-18 E7-MHC-I complexHPV-18 E7 peptide-HLA-A*02:01 complexHuman papillomavirus 18 E7 antigen-MHC complexE7-MHC-I (HPV-18)

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated lysis of tumor cells.