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Gaetano Donofrio"A new oncolytic viral vector for brain gliomas therapy "

Abstract :

Gliomas are devastating tumors of the brain resistant to therapies.
Although some therapies can prolong the survival time of the affected people, gliomas are not curable and new therapeutic approaches need to be investigated. Oncolytic viruses seem to represent an interesting alternative as anticancer agents and new viral agents have to be explored to identify the one with the best characteristics. Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus with a striking tropism and permissive replication toward cancer cells, as well as rat, mouse and human glioma cells. However, BoHV-4 does not replicate into the normal brain parenchyma. The BoHV-4 genome was cloned as a bacterial artificial chromosome to easily manipulatet his large genome and be used as a viral vector platform. In the present paper a herpes simplex virus 1 thymidine kinase suicide gene armed BoHV-4 was constructed, characterized and proven to be highly efficient of killing by apoptosis glioma cells in vitro when co-administered with the pro-drug ganciclovir (GCV). When the armed BoHV-4/GCV therapeutic approach was tested in immuno-competent orthotopic syngenic mouse and rat glioma models in vivo, a significant increase in survival of the treated animals was achieved, where some animals were completely cured. The BoHV-4-based vector represents a promising alternative oncolytic virus for glioma and maybe other types of cancer treatment that merit further investigation.

Selected publications

HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients.Storti P, Donofrio G, Colla S, Airoldi I, Bolzoni M, Agnelli L, Abeltino M, Todoerti K, Lazzaretti M, Mancini C, Ribatti D, Bonomini S, Franceschi V, Pistoia V, Lisignoli G, Pedrazzini A, Cavicchi O, Neri A, Rizzoli V, Giuliani N.Leukemia. 2011 Mar;25(3):527-37. Epub 2010 Nov 23.

Bovine herpesvirus 4 based vector as a potential oncolytic-virus for treatment of glioma.
Redaelli M, Mucignat-Caretta C, Cavaggioni A, Caretta A, D'Avella D, Denaro L, Cavirani S, Donofrio G.Virol J. 2010 Nov 3;7:298.

Giovanni Marsicano