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

Journal of Translational Medicine

Aladar A Szalay²  Peter Michael Jakob³  Ivaylo Gentschev²  Alexa Frentzen²  Christina Kober¹  Prisca Gnamlin¹  Marion Adelfinger¹  Carolin Seubert¹  Ulrike Donat¹  Thomas Christian Basse-Luesebrink³  Elisabeth Hofmann¹  Stephanie Weibel¹ 

[1] Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg D-97074, Germany;Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA;Research Center for Magnetic Resonance Bavaria e.V., Wuerzburg D-97074, Germany

关键词: VEGF;    Lung cancer;    Malignant effusion;    Oncolytic virotherapy;   

Others  :  827625
DOI  :  10.1186/1479-5876-11-106

 received in 2012-08-17, accepted in 2013-04-23,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Weibel et al.; licensee BioMed Central Ltd.

【 图 表 】

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