TY  - JOUR
A1  - Hess, Michael
A1  - Stritzker, Jochen
A1  - Härtl, Barbara
A1  - Sturm, Julia
A1  - Gentschev, Ivaylo
A1  - Szalay, Aladar
T1  - Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies
N2  - 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) 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 cells
KW  - Virologie
KW  - beta-glucuronidase
KW  - oncolytic virus
KW  - cancer
KW  - reporter
KW  - fluorescent probe
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69163
ER  - 
TY  - JOUR
A1  - Gentschev, Ivaylo
A1  - Müller, Meike
A1  - Adelfinger, Marion
A1  - Weibel, Stephanie
A1  - Grummt, Friedrich
A1  - Zimmermann, Martina
A1  - Bitzer, Michael
A1  - Heisig, Martin
A1  - Zhang, Qian
A1  - Yu, Yong A.
A1  - Chen, Nanhai G.
A1  - Stritzker, Jochen
A1  - Lauer, Ulrich M.
A1  - Szalay, Aladar A.
T1  - Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
JF  - PLOS ONE
N2  - Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.
KW  - Breast-tumors
KW  - Nude-mice
KW  - In-vivo
KW  - Cancer
KW  - Inhibitor
KW  - Tissue
KW  - Agent
KW  - COX-2
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135319
VL  - 6
IS  - 7
ER  -