title: Treatment of established lesions caused by high-risk human papilloma virus using a synthetic vaccine.
abstract: Here, we review a novel vaccine modality, characterized by the administration of long (23 to 45 amino acids) synthetic peptides in incomplete Freund's 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 were short major histocompatibility complex class I-binding peptides. Nevertheless, a recent study has shown the clinical efficacy of an anchor-modified short gp100 peptide in melanoma patients. We now review the evidence and mode of action of 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), causing complete regression of all lesions and eradicating virus in 9 of 20 women with high-grade vulvar intraepithelial neoplasia. The nature and strength of the vaccine-induced T-cell response correlated significantly 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 malignant tumors caused by this virus, including HPV16-positive cervical cancer, vulvar cancer, anal cancer, and head and neck cancer.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. c.melief@lumc.nl
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D011817:Rabbits; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
chemical_list: D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic