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

Research

Michael Hess¹  Ulrike Donat¹  Stephanie Weibel¹  Julia B Sturm¹  Jochen Stritzker²  Aladar A Szalay³  Georg Krohne⁴  Nanhai G Chen⁵  Qian Zhang⁵  Yong A Yu⁵  Stepan Gambaryan⁶  Cora Reiss⁶ 

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

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

DOI  :  10.1186/1479-5876-10-9

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

来源: Springer

【 摘 要 】

BackgroundCombination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic.MethodsHere, 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.ResultsWe 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.ConclusionTherefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.

【 授权许可】

Unknown   
© Sturm et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.