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      Regression of Human Prostate Tumors and Metastases in Nude Mice following Treatment with the Recombinant Oncolytic Vaccinia Virus GLV-1h68

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          Abstract

          Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In the current study, we analyzed the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 against two human prostate cancer cell lines DU-145 and PC-3 in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 was able to infect, replicate in, and lyse these prostate cancer cells in culture. In DU-145 and PC-3 tumor xenograft models, a single intravenous injection with GLV-1h68 resulted in a significant reduction of primary tumor size. In addition, the GLV-1h68-infection led to strong inflammatory and oncolytic effects resulting in drastic reduction of regional lymph nodes with PC-3 metastases. Our data documented that the GLV-1h68 virus has a great potential for treatment of human prostate carcinoma.

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          Cancer statistics, 2007.

          Ahmedin Jemal, Rebecca Siegel, Elizabeth Ward … (2007)
          Each year, the American Cancer Society (ACS) estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. This report considers incidence data through 2003 and mortality data through 2004. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,444,920 new cancer cases and 559,650 deaths for cancers are projected to occur in the United States in 2007. Notable trends in cancer incidence and mortality rates include stabilization of the age-standardized, delay-adjusted incidence rates for all cancers combined in men from 1995 through 2003; a continuing increase in the incidence rate by 0.3% per year in women; and a 13.6% total decrease in age-standardized cancer death rates among men and women combined between 1991 and 2004. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. While the absolute number of cancer deaths decreased for the second consecutive year in the United States (by more than 3,000 from 2003 to 2004) and much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress.

            D Kirn, EVANTHIA GALANIS, Ta-Chiang Liu (2007)
            Therapeutic oncolytic viruses (virotherapeutics) constitute a novel class of targeted anticancer agents that have unique mechanisms of action compared with other cancer therapeutics. The development of virotherapeutics has evolved from the use of in vitro-passaged strains (first generation), to genetically engineered selectivity-enhanced viruses (second generation) and finally to genetically engineered transgene-expressing 'armed' oncolytic viruses (third generation). Descriptions of cancer remissions following virus infections date back to a century ago. Initial patient treatment publications, written up to 50 years ago, consisted of case reports or case series of treatment with first-generation, non-engineered viruses. Over the past decade, hundreds of patients with cancer have been treated on prospectively designed clinical trials (including phase III), evaluating over 10 different agents, inlcluding engineered second-generation and third-generation viruses. This Review summarizes and interprets the data from clinical reports over the last century, including safety, efficacy and biological end points (viral and immunologic). Systemic safety and efficiacy has been clearly demonstrated with some virotherapeutics. The implications of these data for future virotherapy development are discussed.
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              Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded.

              Roberto Cattaneo, Tanner C. Miest, Elena Shashkova … (2008)
              Virotherapy is currently undergoing a renaissance, based on our improved understanding of virus biology and genetics and our better knowledge of many different types of cancer. Viruses can be reprogrammed into oncolytic vectors by combining three types of modification: targeting, arming and shielding. Targeting introduces multiple layers of cancer specificity and improves safety and efficacy; arming occurs through the expression of prodrug convertases and cytokines; and coating with polymers and the sequential usage of different envelopes or capsids provides shielding from the host immune response. Virus-based therapeutics are beginning to find their place in cancer clinical practice, in combination with chemotherapy and radiation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Biomed Biotechnol
                Journal ID (publisher-id): JBB
                Title: Journal of Biomedicine and Biotechnology
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1110-7243
                ISSN (Electronic): 1110-7251
                Publication date (Print): 2010
                Publication date (Electronic): 1 April 2010
                Volume: 2010
                Electronic Location Identifier: 489759
                Affiliations
                1Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA
                2Department of Biochemistry, University of Wuerzburg, D-97074 Wuerzburg, Germany
                3Institute for Medical Radiation and Cell Research, University of Wuerzburg, D-97078 Wuerzburg, Germany
                4Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg, D-97078 Wuerzburg, Germany
                5Institute for Molecular Infection Biology, University of Wuerzburg, D-97078 Wuerzburg, Germany
                6Department of Radiation Oncology, Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive 0843, La Jolla, CA 92093-0843, USA
                Author notes
                *Aladar A. Szalay: aaszalay@ 123456genelux.com

                Academic Editor: Colin Cooper

                Article
                DOI: 10.1155/2010/489759
                PMC ID: 2850154
                PubMed ID: 20379368
                SO-VID: 4327b9d1-3357-45e8-a6b9-0b6e6ed6f00d
                Copyright © Copyright © 2010 Ivaylo Gentschev et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 17 July 2009
                Date revision received : 14 October 2009
                Date accepted : 13 January 2010
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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