@article{DonatRotherSchaeferetal.2014, author = {Donat, Ulrike and Rother, Juliane and Sch{\"a}fer, Simon and Hess, Michael and H{\"a}rtl, Barbara and Kober, Christina and Langbein-Laugwitz, Johanna and Stritzker, Jochen and Chen, Nanhai G. and Aguilar, Richard J. and Weibel, Stephanie and Szalay, Alandar A.}, title = {Characterization of Metastasis Formation and Virotherapy in the Human C33A Cervical Cancer Model}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0098533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119674}, pages = {e98533}, year = {2014}, abstract = {More than 90\% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.}, language = {en} } @article{AdelfingerGentschevdeGuibertetal.2014, author = {Adelfinger, Marion and Gentschev, Ivaylo and de Guibert, Julio Grimm and Weibel, Stephanie and Langbein-Laugwitz, Johanna and H{\"a}rtl, Barbara and Escobar, Hugo Murua and Nolte, Ingo and Chen, Nanhai G. and Aguilar, Richard J. and Yu, Yong A. and Zhang, Qian and Frentzen, Alexa and Szalay, Aladar A.}, title = {Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0104337}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119387}, pages = {e104337}, year = {2014}, abstract = {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.}, language = {en} } @article{HessStritzkerHaertletal.2011, author = {Hess, Michael and Stritzker, Jochen and H{\"a}rtl, Barbara and Sturm, Julia and Gentschev, Ivaylo and Szalay, Aladar}, title = {Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69163}, year = {2011}, 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) 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}, subject = {Virologie}, language = {en} }