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.
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.
Nonn
Marion
M
Gynäkologische Molekularbiologie, Universitätsfrauenklinik, Friedrich-Schiller-Universität Jena, Bachstrasse 18, 07743, Jena, Germany.
Schinz
Manuela
M
Zumbach
Klaus
K
Pawlita
Michael
M
Schneider
Achim
A
Dürst
Matthias
M
Kaufmann
Andreas M
AM
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
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