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

TitleExploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2006
AuthorsFranconi, Rosella, Massa Silvia, Illiano E., Muller A., Cirilli A., Accardi L., Di Bonito P., Giorgi C., and Venuti A.
JournalInternational Journal of Immunopathology and Pharmacology
Volume19
Pagination187-197
Keywordsanimal cell, animal experiment, animal model, Animals, Antigens, antineoplastic activity, article, Blotting, cancer immunization, Cancer Vaccines, cellular immunity, controlled study, DNA, drug effect, drug synthesis, enzyme linked immunospot assay, Enzyme-Linked Immunosorbent Assay, Extracellular Space, Female, Human papillomavirus type 16, immunization, Immunoblotting, immunogenicity, Inbred C57BL, Interferon Type II, Mice, mouse, nonhuman, Oncogene Proteins, Papillomaviridae, Plant, Potyvirus, priority journal, protein E7, protein expression, Reverse Transcriptase Polymerase Chain Reaction, secretory vesicle, T-Lymphocytes, Tobacco, tumor cell, tumor growth, tumor volume, vaccine production, Viral, viral gene delivery system, Viral Vaccines, Western
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.

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