Enhancing therapeutic HPV DNA vaccine potency through depletion of CD4+CD25+ T regulatory cells.
Therapeutic human papillomavirus (HPV) vaccines targeting E6 and/or E7 antigens represent an opportunity to control HPV-associated lesions. We have previously generated several therapeutic DNA vaccines targeting HPV-16 E7 antigen and generated significant antitumor effects. Since regulatory T cells (Tregs) play an important role in suppressing immune responses against tumors by immunotherapy, such as DNA vaccines, we tested if the therapeutic effects of a DNA vaccine encoding E7 linked to heat shock protein 70 (Hsp70) can be improved by a strategy to deplete Tregs using a anti-CD25 monoclonal antibody (PC61) in vaccinated mice. We found that administration of PC61 prior to vaccination with E7/Hsp70 DNA was capable of generating higher levels of E7-specific CD8(+) T cells compared to the control antibody, leading to significantly improved therapeutic and long-term protective antitumor effects against an E7-expressing tumor, TC-1. Thus, a strategy to deplete CD4(+)CD25(+) Tregs in conjunction with therapeutic tumor antigen-specific DNA vaccine may represent a potentially promising approach to control tumor. The clinical implications of our study are discussed.
Chuang
Chi-Mu
CM
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Hoory
Talia
T
Monie
Archana
A
Wu
Annie
A
Wang
Mei-Cheng
MC
Hung
Chien-Fu
CF
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000276:immunology*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D019496:Cancer Vaccines; D050884:HSP72 Heat-Shock Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic