HSP70 and modified HPV 16 E7 fusion gene without the addition of a signal peptide gene sequence as a candidate therapeutic tumor vaccine.
Millions of women are currently infected with high-risk human papillomavirus (HPV), which is considered to be a major risk factor for cervical cancer. Thus, it is urgent to develop therapeutic vaccines to eliminate the established infections or HPV-related diseases. In the present study, using the mycobacterium tuberculosis heat shock protein 70 (MtHSP70) gene linked to the modified HPV 16 E7 (mE7) gene, we generated two potential therapeutic HPV DNA vaccines, mE7/MtHSP70 and SigmE7/MtHSP70, the latter was linked to the signal peptide gene sequence of human CD33 at the upstream of the fusion gene. We found that vaccination with the mE7/MtHSP70 DNA vaccine induced a stronger E7-specific CD8+ T cell response and resulted in a more significant therapeutic effect against E7-expressing tumor cells in mice. Our results demonstrated that HSP70 can play a more important role in mE7 and MtHSP70 fusion DNA vaccine without the help of a signal peptide. This may facilitate the use of HSP70 and serve as a significant reference for future study.
Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing 100005, P.R. China.
Jinbao
J
Zong
Changyuan
C
Wang
Qingyong
Q
Wang
Qinglin
Q
Peng
Yufei
Y
Xu
Xixiu
X
Xie
Xuemei
X
Xu
D000818:Animals; D019556:COS Cells; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics*; D002522:Chlorocebus aethiops; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage / Q000235:genetics; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics*
D019496:Cancer Vaccines; D050884:HSP72 Heat-Shock Proteins; D015514:Oncogene Proteins, Fusion; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D019444:Vaccines, DNA