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

Int J Mol Sci. 2024 Apr 11;25(8):4244. doi: 10.3390/ijms25084244.

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.

Keywords: VV-GMCSF-Lact; glioma; oncolytic virus; temozolomide; vaccinia virus.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • Glioma* / drug therapy
  • Glioma* / pathology
  • Glioma* / therapy
  • Granulocyte-Macrophage Colony-Stimulating Factor* / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses* / genetics
  • Temozolomide* / pharmacology
  • Temozolomide* / therapeutic use
  • Vaccinia virus* / genetics
  • Vaccinia virus* / physiology
  • Xenograft Model Antitumor Assays*

Substances

  • Temozolomide
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Antineoplastic Agents
  • CSF2 protein, human