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Published on: April 3, 2018
Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies
Michael Hess1, Jochen Stritzker, Barbara Härtl
1Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany.
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. 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) 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.
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 cells.
Insights
A novel reporter system using bacterial glucuronidase (GusA) enables sensitive detection of oncolytic virus tumor colonization. This GusA marker shows potential for evaluating biological therapies and detecting rare circulating tumor cells.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic viral therapy is a promising cancer treatment modality.
- A need exists for general biomarkers to assess tumor colonization and transgene expression in biological therapies.
Purpose of the Study:
- To establish a reporter gene system for evaluating oncolytic virus therapy.
- To demonstrate the utility of bacterial glucuronidase (GusA) as a reporter.
Main Methods:
- Utilized bacterial glucuronidase (GusA) as a reporter gene within biological therapeutics.
- Employed fluorogenic probes specifically activated by glucuronidase for detection.
Main Results:
- Demonstrated preferential reporter activation within tumors.
- Showed reproducible detection of GusA in serum of treated mice across multiple tumor models.
- Established that GusA detection can differentiate tumor-bearing from healthy mice as early as 9 days post-treatment.
- Confirmed assay sensitivity capable of detecting a single infected tumor cell.
Conclusions:
- Bacterial glucuronidase (GusA) serves as a viable general marker for preclinical and clinical evaluation of biological therapies.
- The GusA system holds potential for detecting rare cells, including circulating tumor cells.
