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  - Adelfinger, Marion
A1  - Gentschev, Ivaylo
A1  - de Guibert, Julio Grimm
A1  - Weibel, Stephanie
A1  - Langbein-Laugwitz, Johanna
A1  - Härtl, Barbara
A1  - Escobar, Hugo Murua
A1  - Nolte, Ingo
A1  - Chen, Nanhai G.
A1  - Aguilar, Richard J.
A1  - Yu, Yong A.
A1  - Zhang, Qian
A1  - Frentzen, Alexa
A1  - Szalay, Aladar A.
T1  - Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy
JF  - PLoS ONE
N2  - Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis.
In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.
KW  - antibodies
KW  - cancer treatment
KW  - carcinomas
KW  - vaccinia virus
KW  - oncolytic viruses
KW  - viral replication
KW  - cell cultures
KW  - enzyme-linked immunoassays
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119387
VL  - 9
IS  - 8
ER  -