title: Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy.
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.
  
  
  CONCLUSIONS
  Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.
authors.affiliation: Department of Biochemistry, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Sturm
authors.forename: Michael
authors.initials: M
authors.lastname: Hess
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weibel
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ulrike
authors.initials: U
authors.lastname: Donat
authors.forename: Cora
authors.initials: C
authors.lastname: Reiss
authors.forename: Stepan
authors.initials: S
authors.lastname: Gambaryan
authors.forename: Georg
authors.initials: G
authors.lastname: Krohne
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007267:Injections; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use / Q000633:toxicity*; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy* / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015850:Interleukin-6; D011994:Recombinant Proteins; D050791:STAT Transcription Factors; D016685:Mitomycin; D053612:Janus Kinases