Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

J Transl Med. 2012 Jan 11:10:9. doi: 10.1186/1479-5876-10-9.

Abstract

Background: Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic.

Methods: Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects.

Results: We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia.

Conclusion: Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Female
  • Gene Expression / drug effects
  • Humans
  • Injections
  • Interleukin-6 / blood
  • Interleukin-6 / pharmacology*
  • Janus Kinases / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Mitomycin / therapeutic use
  • Mitomycin / toxicity*
  • Neoplasms / drug therapy
  • Neoplasms / therapy*
  • Neoplasms / virology*
  • Oncolytic Virotherapy / adverse effects*
  • Recombinant Proteins / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects
  • Vaccinia virus / drug effects
  • Vaccinia virus / physiology*
  • Xenograft Model Antitumor Assays

Substances

  • Interleukin-6
  • Recombinant Proteins
  • STAT Transcription Factors
  • Mitomycin
  • Janus Kinases