Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies

Journal of Translational Medicine

Research

Michael Hess¹  Julia B Sturm¹  Ivaylo Gentschev²  Aladar A Szalay³  Barbara Härtl⁴  Jochen Stritzker⁵ 

[1] Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany;Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany;Genelux Corporation, San Diego, CA, USA;Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany;Genelux Corporation, San Diego, CA, USA;Department of Radiation Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA;Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany;Genelux GmbH, Bernried, Germany;Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany;Genelux GmbH, Bernried, Germany;Genelux Corporation, San Diego, CA, USA;

关键词: beta-glucuronidase;    oncolytic virus;    cancer;    reporter;    fluorescent probe;   

DOI  :  10.1186/1479-5876-9-172

 received in 2011-08-08, accepted in 2011-10-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundOncolytic viral tumor therapy is an emerging field in the fight against cancer with rising numbers of clinical trials and the first clinically approved product (Adenovirus for the treatment of Head and Neck Cancer in China) in this field. Yet, until recently no general (bio)marker or reporter gene was described that could be used to evaluate successful tumor colonization and/or transgene expression in other biological therapies.MethodsHere, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolytic viruses) was used as reporter system.ResultsUsing fluorogenic probes that were specifically activated by glucuronidase we could show 1) preferential activation in tumors, 2) renal excretion of the activated fluorescent compounds and 3) reproducible detection of GusA in the serum of oncolytic vaccinia virus treated, tumor bearing mice in several tumor models. Time course studies revealed that reliable differentiation between tumor bearing and healthy mice can be done as early as 9 days post injection of the virus. Regarding the sensitivity of the newly developed assay system, we could show that a single infected tumor cell could be reliably detected in this assay.ConclusionGusA therefore has the potential to be used as a general marker in the preclinical and clinical evaluation of (novel) biological therapies as well as being useful for the detection of rare cells such as circulating tumor cells.

【 授权许可】

Unknown   
© Hess et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.