Open Access Research

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

Stephanie Weibel1, Elisabeth Hofmann1, Thomas Christian Basse-Luesebrink123, Ulrike Donat1, Carolin Seubert1, Marion Adelfinger1, Prisca Gnamlin1, Christina Kober1, Alexa Frentzen7, Ivaylo Gentschev17, Peter Michael Jakob23 and Aladar A Szalay14567*

Author Affiliations

1 Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg D-97074, Germany

2 Department of Experimental Physics 5, University of Wuerzburg, Wuerzburg D-97074, Germany

3 Research Center for Magnetic Resonance Bavaria e.V., Wuerzburg D-97074, Germany

4 Rudolf Virchow Center, Research Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg D-97078, Germany

5 Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg D-97078, Germany

6 Department of Radiation Medicine and Applied Sciences, UC San Diego Health System, La Jolla, CA 92093, USA

7 Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA

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Journal of Translational Medicine 2013, 11:106  doi:10.1186/1479-5876-11-106

Published: 1 May 2013

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.

Keywords:
Oncolytic virotherapy; Malignant effusion; Lung cancer; VEGF