Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma

Chih-Kwang Sung1, Bryan Choi, Georges Wanna

  • 1Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.

The Laryngoscope
|November 29, 2007
PubMed
Abstract

Insights

Combining oncolytic vesicular stomatitis virus (VSV) with cisplatin showed enhanced squamous cell carcinoma (SCC) tumor cell kill in vitro. In vivo, combination therapy improved rVSV-F efficacy but reduced rVSV-IL12 activity against SCC tumors.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunotherapy
  • Squamous cell carcinoma research

Background:

  • Vesicular stomatitis virus (VSV) exhibits oncolytic properties, selectively targeting tumor cells.
  • Recombinant VSV vectors, rVSV-F and rVSV-IL12, previously showed antitumor effects against squamous cell carcinoma (SCC).
  • Cisplatin is a standard chemotherapeutic agent for SCC.

Purpose of the Study:

  • To evaluate the efficacy of combining cisplatin with rVSV-F and rVSV-IL12 for SCC treatment.
  • To assess the impact of combination therapy on viral replication, tumor cell survival, tumor control, and animal survival.

Main Methods:

  • In vitro studies involved testing rVSV-F and rVSV-IL12 with cisplatin on SCC cell lines, monitoring viral replication and cell viability.
  • In vivo studies utilized an orthotopic murine SCC model, administering intratumoral virus injections combined with systemic cisplatin.
  • Tumor control and animal survival were assessed in the in vivo model.

Main Results:

  • In vitro, the combination of VSV and cisplatin enhanced tumor cell killing without affecting normal human keratinocytes.
  • In vivo, combination therapy with rVSV-F and cisplatin reduced tumor burden and improved survival compared to controls.
  • However, rVSV-IL12 monotherapy demonstrated superior tumor control and survival rates compared to the combination therapy in vivo.

Conclusions:

  • Cisplatin addition did not impede VSV replication or SCC cell killing in vitro.
  • Combination therapy augmented rVSV-F antitumor activity but diminished rVSV-IL12 efficacy in vivo.
  • Further development of viral vectors and combination strategies may offer improved SCC treatments.

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