Targeted therapy of human glioblastoma combining the oncolytic properties of parvovirus H-1 and attenuated strains of the vaccinia virus

Tkacheva A.V.; Sivolobova G.F.; Grazhdantseva A.A.; Shevelev O.B.; Razumov I.A.; Zavjalov E.L.; Loktev V.B.; Kochneva G.V.

doi:https://doi.org/10.17116/molgen20193702183

Tkacheva A.V.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Sivolobova G.F.

State Research Center of Virology and Biotechnology «Vector», 630559, Koltsovo, Russia

Grazhdantseva A.A.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Shevelev O.B.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Razumov I.A.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Zavjalov E.L.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Loktev V.B.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Kochneva G.V.

State Research Center of Virology and Biotechnology «Vector», 630559, Koltsovo, Russia;
Novosibirsk state university, 630090, Novosibirsk, Russia

Targeted therapy of human glioblastoma combining the oncolytic properties of parvovirus H-1 and attenuated strains of the vaccinia virus

Authors:

Tkacheva A.V., Sivolobova G.F., Grazhdantseva A.A., Shevelev O.B., Razumov I.A., Zavjalov E.L., Loktev V.B., Kochneva G.V.

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Journal: Molecular Genetics, Microbiology and Virology. 2019;37(2): 83‑91

DOI: 10.17116/molgen20193702183

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To cite this article:

Tkacheva AV, Sivolobova GF, Grazhdantseva AA, et al. . Targeted therapy of human glioblastoma combining the oncolytic properties of parvovirus H-1 and attenuated strains of the vaccinia virus. Molecular Genetics, Microbiology and Virology. 2019;37(2):83‑91. (In Russ.)
https://doi.org/10.17116/molgen20193702183

Подписка 2026 Молекулярная генетика, микробиология и вирусология (Molecular Genetics, Microbiology and Virology)

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Abstract:

Abstract Both vaccinia virus and rat parvovirus H-1 are currently used to create drugs that have demonstrated their effectiveness against a number of human tumors. In preclinical studies it was demonstrated that the main factor responsible for the oncolytic activity of parvovirus H-1 is the NS1 protein and tumor cells of the brain were especially susceptible to its direct cytotoxic effect. We used NS1 gene insertion to arm two attenuated strains of vaccinia virus for virotherapy of glioblastoma: VV-NS1-dGF and MVA-NS1. Recombinant VV-NS1-dGF was engineered from replicative-competent L-IVP strain attenuated by deletion of the virus growth factor gene. MVA-NS1 was engineered from highly attenuated MVA strain, which is replicative-incompetent for mammalian cells. The NS1 transgene expression significantly enhanced the lytic activity of both recombinants against human U87MG glioblastoma cells regardless of the level of attenuation of the original virus strains in vitro. However, in in vivo experiments, the recombinant VV-NS1-dGF more effectively destroys the subcutaneous xenografts of U87MG cells in Nu/Nu mice compared with the strain MVA-NS1 after a single injection of viruses into the tumor region. Both recombinants selectively replicate in tumor cells, but reproductive capacity of the VV-NS1-dGF is higher, which ensures its rapid accumulation in xenografts and their subsequent destruction. Investigation of the antitumor properties of recombinants in the orthotopic model of U87MG human glioblastoma demonstrated an increase in the lifetime of mice and a significant decrease in tumor volume when treated with VV-NS1-dGF. The data obtained demonstrate that recombinant VV-NS1-dGF has good therapeutic potential against human glioblastoma.

Keywords:

vaccinia virus

parvovirus

recombinant

attenuation

oncolytic viruses

NS1 protein

glioblastoma

Authors:

Tkacheva A.V.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Sivolobova G.F.

State Research Center of Virology and Biotechnology «Vector», 630559, Koltsovo, Russia

Grazhdantseva A.A.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Shevelev O.B.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Razumov I.A.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Zavjalov E.L.

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

Loktev V.B.

State Research Center of Virology and Biotechnology «Vector», Koltsovo, 630559, Novosibirsk, Russia

Kochneva G.V.

State Research Center of Virology and Biotechnology «Vector», 630559, Koltsovo, Russia;
Novosibirsk state university, 630090, Novosibirsk, Russia

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