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

Tahamtan, A ; Sharif University of Technology

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  1. Type of Document: Article
  2. DOI: 10.1186/s12929-014-0069-z
  3. Abstract:
  4. 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
  5. Keywords:
  6. E7 ; Human papilloma virus ; Tumor ; Chitosan ; Gamma interferon ; Interleukin 4 ; Nanocarrier ; Recombinant vaccine ; DNA vaccine ; Oncogene protein E7, Human papillomavirus type 16 ; Protein E7 ; Wart virus vaccine ; Animal cell ; Animal experiment ; Animal model ; Animal tissue ; Antineoplastic activity ; Cancer immunotherapy ; Cancer size ; CD8+ T lymphocyte ; Cell count ; CHO cell line ; Controlled study ; Cytokine production ; Cytokine response ; Cytotoxic T lymphocyte ; Cytotoxicity ; Female ; Genetic transfection ; Human papillomavirus type 16 ; Immune response ; In vitro study ; Lymphocyte proliferation ; Mouse ; Nonhuman ; Particle size ; Uterine cervix cancer ; Zeta potential ; Animal ; Drug delivery system ; Human ; Immunology
  7. Source: Journal of Biomedical Science ; Vol. 21, issue. 1 , July , 2014 ; ISSN: 10217770
  8. URL: http://www.jbiomedsci.com/content/21/1/69