title: Synthetic vaccine for the treatment of lesions caused by high risk human papilloma virus.
abstract: Until recently, therapeutic cancer vaccines only sporadically led to long-term clinical responses. We here report on a novel vaccine modality, characterized by the administration of long (23-45 amino acids) synthetic peptides in incomplete Freund adjuvant (mineral oil-based, Montanide ISA-51), delivered subcutaneously. Such vaccines were first demonstrated to be much more potent in preclinical T-cell response induction and tumor therapy experiments than short major histocompatibility complex class I-binding peptides that have been used extensively in the clinic. A long-peptide vaccine consisting of 13 overlapping peptides, together covering the entire length of the 2 oncogenic proteins E6 and E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression of all lesions and eradication of virus in 9 of 20 women with high-grade vulvar intraepithelial neoplasia. The nature and strength of the vaccine-induced T-cell response were significantly correlated with the clinical response. This vaccine promises to be of use, not only in patients with premalignant lesions caused by high-risk HPV16, but also in patients with malignant tumors caused by this virus, including HPV16-positive cervical cancer, anal cancer, and head and neck cancer.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands. C.Melief@lumc.nl
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000628:therapy / Q000821:virology; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000627:therapeutic use; D002578:Uterine Cervical Dysplasia / Q000628:therapy / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16