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

Journal of Translational Medicine

Aladar A Szalay⁴  Jochen Stritzker¹  Georg Krohne²  Stepan Gambaryan³  Cora Reiss³  Ulrike Donat⁵  Qian Zhang⁴  Yong A Yu⁴  Nanhai G Chen⁴  Stephanie Weibel⁵  Michael Hess⁵  Julia B Sturm⁵ 

[1] Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA;Division of Electron Microscopy, University of Würzburg, 97074 Würzburg, Germany;Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany;Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California San Diego, La Jolla, CA 92093, USA;Department of Biochemistry, University of Würzburg, 97074 Würzburg, Germany

关键词: chemotherapy;    oncolysis;    hyper-IL-6;    cytokine;    cancer;    vaccinia virus;   

Others  :  1207786
DOI  :  10.1186/1479-5876-10-9

 received in 2011-11-04, accepted in 2012-01-11,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Sturm et al; licensee BioMed Central Ltd.

【 图 表 】

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