DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens generates more potent immunotherapeutic effects than respective E6 or E7 tumor antigens.
OBJECTIVE
Vaccination based on tumor antigen is an attractive strategy for cancer prevention and therapy. Cervical cancer is highly associated with human papillomavirus, especially type 16. We developed DNA vaccines encoding heat shock protein 60 (HSP60) linked to HPV16 E6 or E7 to test if HSP60 chimeric DNA vaccines may generate strong E6 and/or E7-specific immune response and anti-tumor effects in vaccinated mice.


METHODS
In vivo antitumor effects such as preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays such as intracellular cytokine stainings, ELISA for Ab responses, and direct and cross-priming effects, were also performed.


RESULTS
HSP60 chimeric DNA vaccines generated strong E6- or E7-specific immune responses and anti-tumor effects in vaccinated mice via direct and cross-priming effects. HSP60 was also linked with both E6 and E7 antigens and the HSP60/E6/E7 chimeric DNA vaccine generated more potent immunotherapeutic effects on E6- and E7-expressing tumors than HSP60/E6 or HSP60/E7 chimeric DNA vaccine alone.


CONCLUSIONS
Utilization of both E6 and E7 tumor antigens can advance the therapy of tumors associated with HPV-infections. The DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens can generate more potent immunotherapeutic effects than E6 or E7 tumor antigens alone.
Huang
Chia-Yen
CY
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Chi-An
CA
Lee
Chien-Nan
CN
Chang
Ming-Cheng
MC
Su
Yi-Ning
YN
Lin
Yi-Chun
YC
Hsieh
Chang-Yao
CY
Cheng
Wen-Fang
WF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D018834:Chaperonin 60; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D004247:DNA