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 language | English |
|---|---|
| Pages (from-to) | 187-197 |
| Number of pages | 11 |
| Journal | International Journal of Immunopathology and Pharmacology |
| Volume | 19 |
| Issue number | 1 |
| Publication status | Published - Jan 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Exploiting the plant secretory pathway to improve the anti-cancer activity of a plant-derived HPV16 E7 vaccine
AU - Franconi, R.
AU - Massa, S.
AU - Illiano, E.
AU - Muller, A.
AU - Cirilli, A.
AU - Accardi, L.
AU - Di Bonito, P.
AU - Giorgi, C.
AU - Venuti, A.
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
KW - Cancer immunotherapy
KW - Human papilloma virus
KW - Plant
KW - Plant signal peptide
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=33646264541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646264541&partnerID=8YFLogxK
M3 - Article
C2 - 16569357
AN - SCOPUS:33646264541
VL - 19
SP - 187
EP - 197
JO - International Journal of Immunopathology and Pharmacology
JF - International Journal of Immunopathology and Pharmacology
SN - 0394-6320
IS - 1
ER -