Antitumor effect of therapeutic HPV DNA vaccines with chitosan-based nanodelivery systems

J Biomed Sci. 2014 Jul 31;21(1):69. doi: 10.1186/s12929-014-0069-z.

Abstract

Background: Cervical cancer is the second-most-common cause of malignancies in women worldwide, and the oncogenic activity of the human papilloma virus types (HPV) E7 protein has a crucial role in anogenital tumors. In this study, we have designed a therapeutic vaccine based on chitosan nanodelivery systems to deliver HPV-16 E7 DNA vaccine, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer. We have developed a Nano-chitosan (NCS) as a carrier system for intramuscular administration using a recombinant DNA vaccine expressing HPV-16 E7 (NCS-DNA E7 vaccine). NCS were characterized in vitro for their gene transfection ability.

Results: The transfection of CS-pEGFP NPs was efficient in CHO cells and the expression of green fluorescent proteins was well observed. In addition, NCS-DNA E7 vaccine induced the strongest E7-specific CD8+ T cell and interferon γ responses in C57BL/6 mice. Mice vaccinated with NCS-DNA E7 vaccine were able to generate potent protective and therapeutic antitumor effects against challenge with E7-expressing tumor cell line, TC-1.

Conclusions: The strong therapeutic effect induced by the Chitosan-based nanodelivery suggest that nanoparticles may be an efficient carrier to improve the immunogenicity of DNA vaccination upon intramuscular administration and the platform could be further exploited as a potential cancer vaccine candidate in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chitosan / pharmacology*
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mice
  • Papillomavirus E7 Proteins* / immunology
  • Papillomavirus E7 Proteins* / pharmacology
  • Papillomavirus Vaccines* / immunology
  • Papillomavirus Vaccines* / pharmacology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology
  • Vaccination
  • Vaccines, DNA* / immunology
  • Vaccines, DNA* / pharmacology

Substances

  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Vaccines, DNA
  • oncogene protein E7, Human papillomavirus type 16
  • Chitosan