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Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer

Please always quote using this URN: urn:nbn:de:bvb:20-opus-96016
  • 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 malignantBackground 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.show moreshow less

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Metadaten
Author: Aladar A Szalay, Stephanie Weibel, Elisabeth Hofmann, Thomas Christian Basse-Luesebrink, Ulrike Donat, Carolin Seubert, Marion Adelfinger, Prisca Gnamlin, Christina Kober, Alexa Frentzen, Ivaylo Gentschev, Peter Michael Jakob
URN:urn:nbn:de:bvb:20-opus-96016
Document Type:Journal article
Faculties:Fakultät für Physik und Astronomie / Physikalisches Institut
Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie
Language:English
Parent Title (English):Journal of Translational Medicine
Year of Completion:2013
Source:In: Journal of Translational Medicine (2013) 11: 106, doi:10.1186/1479-5876-11-106
URL:http://www.translational-medicine.com/content/11/1/106
DOI:https://doi.org/doi:10.1186/1479-5876-11-106
Sonstige beteiligte Institutionen:MRB Forschungszentrum für Magnet-Resonanz-Bayern e.V., Am Hubland, D-97074 Würzburg
Sonstige beteiligte Institutionen:Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Lungenkrebs; Vascular endothelial Growth Factor
Tag:Lung cancer; Malignant effusion; Oncolytic virotherapy; VEGF
Release Date:2014/04/23
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2013
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung