title: Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer.
abstract: BACKGROUND
  Malignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options.
  
  
  METHODS
  In this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma.
  
  
  RESULTS
  We demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment.
  
  
  CONCLUSIONS
  Here, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer.
authors: Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg D-97074, Germany.
authors: Stephanie
authors: S
authors: Weibel
authors: Elisabeth
authors: E
authors: Hofmann
authors: Thomas Christian
authors: TC
authors: Basse-Luesebrink
authors: Ulrike
authors: U
authors: Donat
authors: Carolin
authors: C
authors: Seubert
authors: Marion
authors: M
authors: Adelfinger
authors: Prisca
authors: P
authors: Gnamlin
authors: Christina
authors: C
authors: Kober
authors: Alexa
authors: A
authors: Frentzen
authors: Ivaylo
authors: I
authors: Gentschev
authors: Peter Michael
authors: PM
authors: Jakob
authors: Aladar A
authors: AA
authors: Szalay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000628:therapy*; D057127:Single-Chain Antibodies / Q000737:chemistry; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D057127:Single-Chain Antibodies; D042461:Vascular Endothelial Growth Factor A
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