Mutants of plant genes for developing cancer vaccines.
Preventive Human Papillomavirus (HPV) vaccination is an expensive practice and it may be an insufficient tool to tackle cervical cancer worldwide. Therapeutic intervention is seeking for safe/effective vaccines inducing the activation of CD8+ cytotoxic T lymphocytes (CTLs) that is required to clear the tumor. Linking a tumor-specific antigen (i.e. the E7 oncoprotein of the 'high risk' HPVs) to molecules able to increase its immune 'visibility' represents a strategy to force the immune system to fight cancer. We focused on plants as sources of innovative immunostimulatory sequences. We have already shown the anti-cancer activity obtained by fusing E7GGG (a mutagenized E7 gene from the high risk HPV type 16) to the coat protein of a plant virus, the Potato Virus X. We are now investigating plant-derived carriers, such as the 'Ribosome inactivating proteins' (RIPs), so far used to develop immunotoxins for targeted cancer therapy. Beside toxicity, RIPs have other features (i.e. immunogenicity, ability to modulate immune functions and apoptosis induction) that could be useful tools to use in tumor immunotherapy. A non toxic mutant of saporin (SAP-KQ) was used as a carrier for the E7GGG gene in the context of a DNA-based vaccine. We show here that fusion constructs of SAP-KQ with E7GGG can induce E7-specific Immunoglobulins (IgGs), CTLs and Delayed-Type Hypersensitivity (DTH) affecting the growth of E7-expressing tumors in mice. These data demonstrate that mutant plant genes hold promise to improve the poor immunogenicity of tumor-associated cancer antigens and could contribute to the evolution of new cancer immunotherapy.
ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, CR Casaccia, UT BIORAD-FARM, Rome, Italy.
Silvia
S
Massa
Francesca
F
Paolini
Laura
L
Spanò
Rosella
R
Franconi
Aldo
A
Venuti
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control; D027383:Papillomaviridae / Q000235:genetics; D053918:Papillomavirus Vaccines / Q000235:genetics* / Q000276:immunology*; D030821:Plants, Genetically Modified / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics*; D012376:Rodent Diseases / Q000473:pathology / Q000517:prevention & control; D000076985:Saporins
D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins