@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{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{WangChenMinevetal.2013, author = {Wang, Huiqiang and Chen, Nanhai G. and Minev, Boris R. and Zimmermann, Martina and Aguilar, Richard J. and Zhang, Qian and Sturm, Julia B. and Fend, Falko and Yu, Yong A. and Cappello, Joseph and Lauer, Ulrich M. and Szalay, Aladar A.}, title = {Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0071105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130059}, pages = {e71105}, year = {2013}, abstract = {Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.}, language = {en} }