Avirulent herpetic viruses useful as tumoricidal agents and...

C - Chemistry – Metallurgy – 12 – N

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C12N 7/04 (2006.01) A61K 35/76 (2006.01) A61K 39/245 (2006.01) C12N 7/00 (2006.01) C12N 7/01 (2006.01)

Patent

CA 2227860

Isolated tumoricidal herpetic viruses, in particular neurotrophic herpes viruses, T-lymphotrophic viruses, and B-lymphotrophic viruses, which are avirulent and capable of selectively replicating in and destroying neoplastic cells, and pharmaceutical compositions, vaccines, and methods of destroying neoplastic cells employing the isolated tumoricidal herpetic viruses are described. A method of isolating tumoricidal herpetic viruses by sequentially passaging attenuated, avirulent herpetic viruses on neoplastic cells which fail to support replication of the herpetic viruses and isolating the viruses which grow on the neoplastic cells is also described. Herpes simplex virus mutants having a genome from which the .gamma.34.5 genes have been deleted and which require at least one additional mutation to produce a non-neurovirulent herpes simplex virus which selectively replicates in and destroys neoplastic cells are also described.

Virus herpétiques tumoricides isolés. Il s'agit notamment des virus neurotrophiques de l'herpès, des virus T-lymphotrophiques et des virus B-lymphotrophiques, qui sont avirulents et susceptibles de se reproduire sélectivement dans des cellules néoplasiques et de les détruire. L'invention concerne aussi des compositions pharmaceutiques, des vaccins et des techniques de destruction de cellules néoplasiques faisant appel à ces virus herpétiques tumoricides isolés. Est également décrite une technique d'isolation de virus herpétiques tumoricides consistant à faire passer séquentiellement des virus herpétiques avirulents atténués sur des cellules néoplasiques qui ne permettent pas la reproduction des virus herpétiques et à isoler les virus qui se développent sur les cellules néoplasiques. Sont aussi décrits des mutants du virus d'Herpes simplex possédant un génome dont les gènes .gamma.34.5 ont été éliminés et qui nécessitent au moins une mutation de plus pour produire un virus non neurovirulent d'Herpes simplex susceptible de se reproduire sélectivement dans des cellules néoplasiques et de les détruire.

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