Exploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine

R. Franconi, S. Massa, E. Illiano, A. Muller, A. Cirilli, L. Accardi, P. Di Bonito, C. Giorgi, A. Venuti

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Abstract

The human papillomavirus 16 (HPV16) E7 oncoprotein can be considered a 'tumor-specific antigen' and, therefore, it represents a promising target for a therapeutic vaccine against HPV-associated tumors. Efficient production of E7 protein with a plant-based transient expression system has been already described and it was demonstrated that E7-containing crude plant extracts confer partial protection against tumor challenge in a mouse model system. Before adopting the plant-based system as a cost-effective method for the production of an E7-based anti-cancer vaccine, some aspects, such as the oncoprotein yield, need further investigation. In the present study, we report the transient expression, mediated by a potato virus X (PVX)-derived vector, of the E7 protein targeted to the secretory system of Nicotiana benthamiana plants by using a plant-derived signal sequence. Targeting the antigen to the secretory pathway enhanced the E7 protein expression levels about five-fold. Mice immunized by s.c. administration with crude foliar extracts containing E7 showed strong stimulation of cell-mediated immune response after five boosters, as detected by ELISPOT. After challenging with the E7-expressing C3 tumor cells, tumor growth was completely inhibited in 80% of the vaccinated animals and a drastic reduction of tumor burden was observed in the remaining tumor-affected mice. These data demonstrate that, by enhancing E7 yield, it is possible to improve the anti-cancer activity of the plant-based experimental vaccine and open the way for a large-scale production of the E7 protein which could be purified or used as 'in planta' formulation, also suitable for oral therapeutic vaccination. Copyright © by Biolife, s.a.s.
Original languageEnglish
Pages (from-to)187 - 197
Number of pages11
JournalInternational Journal of Immunopathology and Pharmacology
Volume19
Issue number1
Publication statusPublished - Jan 2006
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Franconi, R., Massa, S., Illiano, E., Muller, A., Cirilli, A., Accardi, L., ... Venuti, A. (2006). Exploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine. International Journal of Immunopathology and Pharmacology, 19(1), 187 - 197.