Anti-tumor effects of genetic vaccines against HPV major oncogenes

Marcelo Nazário Cordeiro, Francesca Paolini, Silvia Massa, Gianfranca Curzio, Elena Illiano, Anna Jéssica Duarte Silva, Rosella Franconi, Massimiliano Bissa, Carlo De Giuli Morghen, Antonio Carlos De Freitas, Aldo Venuti

Research output: Contribution to journalArticle

Abstract

Expression of HPV E5, E6 and E7 oncogenes are likely to overcome the regulation of cell proliferation and to escape immunological control, allowing uncontrolled growth and providing the potential for malignant transformation. Thus, their three oncogenic products may represent ideal target antigens for immunotherapeutic strategies. In previous attempts, we demonstrated that genetic vaccines against recombinant HPV16 E7 antigen were able to affect the tumor growth in a pre-clinical mouse model. To improve this anti-HPV strategy we developed a novel approach in which we explored the effects of E5-based genetic immunization. We designed novel HPV16 E5 genetic vaccines based on two different gene versions: whole E5 gene and E5Multi. The last one is a long multi epitope gene designed as a harmless E5 version. Both E5 genes were codon optimized for mammalian expression. In addition, we demonstrated that HPV 16 E5 oncogene is expressed in C3 mouse cell line making it an elective model for the study of E5 based vaccine. In this mouse model the immunological and biological activity of the E5 vaccines were assessed in parallel with the activity of anti-E7 and anti-E6 vaccines already reported to be effective in an immunotherapeutic setting. These E7 and E6 vaccines were made with mutated oncogenes, the E7GGG mutant that does not bind pRb and the E6F47R mutant that is less effective in inhibiting p53, respectively. Results confirmed the immunological activity of genetic formulations based on attenuated HPV16 oncogenes and showed that E5-based genetic immunization provided notable anti-tumor effects.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalHuman Vaccines and Immunotherapeutics
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • C3 cell line
  • DNA vaccines
  • HPV16 E5
  • Human papillomavirus
  • Immunologic response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Fingerprint Dive into the research topics of 'Anti-tumor effects of genetic vaccines against HPV major oncogenes'. Together they form a unique fingerprint.

  • Cite this

    Cordeiro, M. N., Paolini, F., Massa, S., Curzio, G., Illiano, E., Silva, A. J. D., Franconi, R., Bissa, M., De Giuli Morghen, C., De Freitas, A. C., & Venuti, A. (2015). Anti-tumor effects of genetic vaccines against HPV major oncogenes. Human Vaccines and Immunotherapeutics, 11(1), 45-52. https://doi.org/10.4161/hv.34303