The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma

Author:

Vasileva Natalia12ORCID,Ageenko Alisa1ORCID,Byvakina Arina1ORCID,Sen’kova Aleksandra1ORCID,Kochneva Galina3ORCID,Mishinov Sergey4ORCID,Richter Vladimir1,Kuligina Elena12ORCID

Affiliation:

1. Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave, 8, Novosibirsk 630090, Novosibirsk Region, Russia

2. “Oncostar” LLC, Inzhenernaya Street 23, Novosibirsk 630090, Novosibirsk Region, Russia

3. The State Research Center of Virology and Biotechnology “VECTOR”, Koltsovo 630559, Novosibirsk Region, Russia

4. Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Frunze Street 17, Novosibirsk 630091, Novosibirsk Region, Russia

Abstract

Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide.

Funder

Russian state-funded project for ICBFM SB RAS

Publisher

MDPI AG

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