Combined VSV Oncolytic Virus and Chemotherapy for Squamous Cell Carcinoma

Authors

  • Chih-Kwang Sung MD, MS,

    1. From the Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York, USA
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  • Bryan Choi MS,

    1. From the Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York, USA
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  • Georges Wanna MD,

    1. From the Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York, USA
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  • Eric M. Genden MD,

    1. From the Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York, USA
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  • Savio L. C. Woo PhD,

    1. Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, USA
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  • Edward J. Shin MD

    Corresponding author
    1. From the Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York, USA
    • Edward J. Shin, MD, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1189, New York, NY 10029, U.S.A.
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  • Presented (podium presentation) at the Triological Society meeting at COSM, San Diego, California, U.S.A. April 28, 2007.

  • Source of financial support or funding: Department of Otolaryngology–Head and Neck Surgery, Mount Sinai School of Medicine, New York, NY, USA.

Abstract

Objectives: Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy.

Study Design: In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival.

Results: In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy.

Conclusions: Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.

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