title: Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany.
authors: Michael
authors: M
authors: Hess
authors: Jochen
authors: J
authors: Stritzker
authors: Barbara
authors: B
authors: Härtl
authors: Julia B
authors: JB
authors: Sturm
authors: Ivaylo
authors: I
authors: Gentschev
authors: Aladar A
authors: AA
authors: Szalay
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology*; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology / Q000652:urine / Q000821:virology; D050130:Oncolytic Virotherapy; D013379:Substrate Specificity; D013997:Time Factors; D014616:Vaccinia virus / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005456:Fluorescent Dyes; D005966:Glucuronidase