Human HSP70 and modified HPV16 E7 fusion DNA vaccine induces enhanced specific CD8+ T cell responses and anti-tumor effects.
Cervical cancer is one of the most common cancers in women worldwide and persistent infection with human papilloma virus (HPV)s is considered to be the major risk factor. Millions of women are currently infected with high risk genotypes. Therefore, it is imperative to develop therapeutic vaccines to eliminate established infection or HPV-related disease. In the current study, we generated two potential therapeutic HPV DNA vaccines, SigmE7/MtHSP70 and SigmE7/HuHSP70, using human and mycobacterium tuberculosis HSP70 linked, respectively, to HPV16 mE7 and the signal peptide gene of human CD33. Our comparative evaluation of these two vaccines found that vaccination with the SigmE7/HuHSP70 DNA vaccine induced a stronger E7-specific CD8+ T cell immune response and resulted in a more significant therapeutic effect against E7 expressing tumor cells. Our study may serve as an important foundation and significant reference for future clinical applications.
Zong
Jinbao
J
Department of Biophysics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
Peng
Qinglin
Q
Wang
Qingyong
Q
Zhang
Ting
T
Fan
Dongsheng
D
Xu
Xuemei
X
D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology
D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16