title: Dendritic cell-based tumor vaccine for cervical cancer I: in vitro stimulation with recombinant protein-pulsed dendritic cells induces specific T cells to HPV16 E7 or HPV18 E7.
abstract: OBJECTIVE
  Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancers. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded dendritic cells (DC) were evaluated as cellular tumor vaccine.
  
  
  METHODS
  Autologous monocyte-derived DCs loaded with recombinant HPV16 or HPV18 E7 oncoprotein were used to induce in vitro a specific T cell response. Specificities of activated T cells were determined.
  
  
  RESULTS
  E7-specific T cells could be identified in 18/20 T cell lines from healthy blood donors. CD4(+) T cell responses (13/16) were found by proliferation assay. CD8(+) CTLs (12/18) were detectable by interferon-gamma (IFN-gamma) ELISpot analysis. Seven donors reacted in both assays and only 2/20 T cell lines did not react in any assay. Thus, specific T cells could be activated in >80% of healthy individuals. T cell lines from suitable donors were specific for HLA-A*0201-restricted epitopes. Furthermore, HPV E7 antigen-loaded DC stimulated specific responses in freshly isolated tumor infiltrating lymphocyte (TIL) populations of cervical cancer patients.
  
  
  CONCLUSIONS
  Autologous dendritic cells loaded with HPV E7 protein can induce T cell responses in healthy individuals by in vitro stimulation and evoke responses in TIL from cervical cancer biopsies. Since there are no limitations with respect to specific HLA-haplotypes, these findings may be a basis for the development of a therapeutic protein-based DC tumor vaccine against cervical cancer for HPV16- and HPV18-positive patients.
authors.affiliation: Gynäkologische Molekularbiologie, Universitätsfrauenklinik, Friedrich-Schiller-Universität Jena, Bachstrasse 18, 07743, Jena, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Nonn
authors.forename: Manuela
authors.initials: M
authors.lastname: Schinz
authors.forename: Klaus
authors.initials: K
authors.lastname: Zumbach
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Achim
authors.initials: A
authors.lastname: Schneider
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
mesh_terms: D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000494:pharmacology; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology; D020551:Pulse Therapy, Drug; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000150:complications / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology*; D014765:Viral Vaccines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16