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Updated: Oct 15, 2025
Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Double Recombinant Vaccinia Virus: A Candidate Drug against Human Glioblastoma
Natalia Vasileva1,2, Alisa Ageenko1, Maria Dmitrieva1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, 630090 Novosibirsk, Russia.
Abstract:
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.
Insights
VV-GMCSF-Lact, a novel oncolytic virus, shows promise for treating aggressive glioblastoma. This engineered vaccinia virus effectively reduces glioblastoma cell viability and inhibits tumor growth in preclinical models.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Glioblastoma is an aggressive brain tumor with a poor prognosis, necessitating innovative treatment strategies.
- Virotherapy, using viruses to target cancer cells, is a rapidly advancing field in oncological research.
- Existing treatments for glioblastoma have limited efficacy, highlighting the need for novel therapeutic approaches.
Purpose of the Study:
- To evaluate the therapeutic potential of VV-GMCSF-Lact as a treatment for glioblastoma.
- To assess the efficacy of VV-GMCSF-Lact against glioblastoma cells in vitro and in vivo.
- To determine the ability of VV-GMCSF-Lact to cross the blood-brain barrier and target glioblastoma xenografts.
Main Methods:
- VV-GMCSF-Lact, a recombinant vaccinia virus, was engineered with specific gene deletions and insertions.
- In vitro studies assessed the cytotoxic activity of VV-GMCSF-Lact against various glioblastoma cell lines.
- In vivo studies involved orthotopic transplantation of human glioblastoma in animal models to evaluate therapeutic efficacy after intravenous and intratumoral administration.
Main Results:
- VV-GMCSF-Lact demonstrated significant reduction in glioblastoma cell viability in vitro.
- The engineered virus effectively crossed the blood-brain barrier in preclinical models.
- Intravenous and intratumoral administration of VV-GMCSF-Lact inhibited the growth of glioblastoma xenografts and reduced metastasis.
Conclusions:
- VV-GMCSF-Lact exhibits potent anti-glioblastoma activity, making it a promising candidate for further clinical development.
- The virus's ability to target glioblastoma cells and overcome the blood-brain barrier supports its potential as a novel therapeutic agent.
- These findings suggest that VV-GMCSF-Lact-based virotherapy could offer a new treatment avenue for patients with glioblastoma.
