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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalInternational Journal of Immunopathology and Pharmacology
Volume19
Issue number1
Publication statusPublished - Jan 2006

Fingerprint

Human papillomavirus 16
Secretory Pathway
Vaccines
Neoplasms
Oncogene Proteins
Complex Mixtures
Proteins
Potexvirus
Enzyme-Linked Immunospot Assay
Papillomavirus Vaccines
Cancer Vaccines
Plant Extracts
Neoplasm Antigens
Protein Sorting Signals
Tumor Burden
Tobacco
Vaccination
Antigens
Costs and Cost Analysis
Therapeutics

Keywords

  • Cancer immunotherapy
  • Human papilloma virus
  • Plant
  • Plant signal peptide
  • Vaccine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Exploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine. / Franconi, R.; Massa, S.; Illiano, E.; Muller, A.; Cirilli, A.; Accardi, L.; Di Bonito, P.; Giorgi, C.; Venuti, A.

In: International Journal of Immunopathology and Pharmacology, Vol. 19, No. 1, 01.2006, p. 187-197.

Research output: Contribution to journalArticle

Franconi, R, Massa, S, Illiano, E, Muller, A, Cirilli, A, Accardi, L, Di Bonito, P, Giorgi, C & 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, vol. 19, no. 1, pp. 187-197.
Franconi, R. ; Massa, S. ; Illiano, E. ; Muller, A. ; Cirilli, A. ; Accardi, L. ; Di Bonito, P. ; Giorgi, C. ; Venuti, A. / Exploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine. In: International Journal of Immunopathology and Pharmacology. 2006 ; Vol. 19, No. 1. pp. 187-197.
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