Double Recombinant Vaccinia Virus: A Candidate Drug against Human Glioblastoma
Natalia Vasileva,
Alisa Ageenko,
Maria Dmitrieva,
Anna Nushtaeva,
Sergey Mishinov,
Galina Kochneva,
Vladimir Richter,
Elena Kuligina
Affiliations
Natalia Vasileva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Alisa Ageenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Maria Dmitrieva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Anna Nushtaeva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Sergey Mishinov
Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Department of Neurosurgery, Frunze Street 17, 630091 Novosibirsk, Russia
Galina Kochneva
The State Research Center of Virology and Biotechnology “VECTOR”, Department of Molecular Virology of Flaviviruses and Viral Hepatitis, Novosibirsk Region, 630559 Koltsovo, Russia
Vladimir Richter
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Elena Kuligina
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia
Glioblastoma is one of the most aggressive brain tumors. Given the poor prognosis of this disease, novel methods for glioblastoma treatment are needed. Virotherapy is one of the most actively developed approaches for cancer therapy today. VV-GMCSF-Lact is a recombinant vaccinia virus with deletions of the viral thymidine kinase and growth factor genes and insertions of the granulocyte–macrophage colony-stimulating factor and oncotoxic protein lactaptin genes. The virus has high cytotoxic activity against human cancer cells of various histogenesis and antitumor efficacy against breast cancer. In this work, we show VV-GMCSF-Lact to be a promising therapeutic agent for glioblastoma treatment. VV-GMCSF-Lact effectively decreases the viability of glioblastoma cells of both immortalized and patient-derived cultures in vitro, crosses the blood–brain barrier, selectively replicates into orthotopically transplanted human glioblastoma when intravenously injected, and inhibits glioblastoma xenograft and metastasis growth when injected intratumorally.
