title: Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the safety of the administration of a bacterial expression plasmid encoding a 13 amino acid sequence that is highly homologous with human papillomavirus E7 within poly (lactide-co-glycolide) microparticles (ZYC101) in women with HLA A2+ antigen and persistent cervical intraepithelial neoplasia grade 2/3 and human papillomavirus 16.
  
  
  METHODS
  Fifteen women entered an institutional review board-approved dose-escalating phase I study with the use of three levels of blood monitoring and urine studies, Papanicolaou tests, and colposcopy. Escalation required no serious adverse events. Immunologic responses were evaluated in peripheral blood with the use of human papillomavirus peptide-stimulated interferon gamma enzyme-linked immunosorbent assay for T-cell reactivity. In cervical secretions, immunoglobulin A anti-human papillomavirus 16 E2 concentrations were measured. Three doses every 3 weeks were followed 4 weeks later by surgical excision.
  
  
  RESULTS
  No serious adverse events occurred. Five women had complete histologic responses; 11 women had human papillomavirus-specific T-cell responses. Four of five complete histologic responses developed immunoglobulin A anti-E2-specific antibody.
  
  
  CONCLUSIONS
  ZYC101 warrants further investigation because of a 33% complete histologic responses, a 73% immunologic response, and no serious adverse events.
authors.affiliation: Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA. esheets@partners.org
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Sheets
authors.forename: Robert G
authors.initials: RG
authors.lastname: Urban
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
authors.forename: Mary Lynne
authors.initials: ML
authors.lastname: Hedley
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Politch
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: Laila I
authors.initials: LI
authors.lastname: Muderspach
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Cole
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Crowley-Nowick
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000235:genetics*; D002214:Capsules; D004279:DNA, Viral / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004598:Electrosurgery; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D010316:Particle Size; D010957:Plasmids; D010958:Plasminogen; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D014771:Virion; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D002214:Capsules; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C076036:oncogene protein E2, Human papillomavirus type 1; C059731:oncogene protein E7, Human papillomavirus type 16; D010958:Plasminogen