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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-75224
  • 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 cellBackground: 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.show moreshow less

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Metadaten
Author: Julia B. Sturm, Michael Hess, Stephanie Weibel, Nanhei G. Chen, Yong A. Yu, Quian Zhang, Ulrike Donat, Cora Reiss, Stepan Gambaryan, Georg Krohne, Jochen Stritzker, Aladar A. Szalay
URN:urn:nbn:de:bvb:20-opus-75224
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Year of Completion:2012
Source:In: Journal of Translational Medicine (2012) 10: 9, doi:10.1186/1479-5876-10-9
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
GND Keyword:Biologie
Tag:cancer; chemotherapy; cytokine; hyper-IL-6; oncolysis; vaccinia virus
Release Date:2013/03/16
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2012
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung