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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-69163
  • Background: Oncolytic 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. Methods: Here, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolyticBackground: Oncolytic 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. Methods: Here, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolytic viruses) was used as reporter system. Results: Using fluorogenic probes that were specifically activated by glucuronidase we could show 1) preferential activation in tumors, 2) rena l 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. Conclusion: GusA 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 cellsshow moreshow less

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Metadaten
Author: Michael Hess, Jochen Stritzker, Barbara Härtl, Julia Sturm, Ivaylo Gentschev, Aladar Szalay
URN:urn:nbn:de:bvb:20-opus-69163
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Year of Completion:2011
Source:In: Journal of Translational Medicine (2011) 9:172, doi:10.1186/1479-5876-9-172
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Virologie
Tag:beta-glucuronidase; cancer; fluorescent probe; oncolytic virus; reporter
Release Date:2012/11/26
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2011
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung