The Experts below are selected from a list of 3903 Experts worldwide ranked by ideXlab platform
Liliana María Elena Finocchiaro - One of the best experts on this subject based on the ideXlab platform.
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Cytokine-enhanced vaccine and Suicide Gene Therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
Cancer gene therapy, 2012Co-Authors: Liliana María Elena Finocchiaro, Gerardo C. GlikinAbstract:Cytokine-enhanced vaccine and Suicide Gene Therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
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Suicide Gene Therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro
Gene therapy, 2009Co-Authors: María L. Gil-cardeza, Marcela Solange Villaverde, Gabriel L. Fiszman, N A Altamirano, R A Cwirenbaum, Gerardo C. Glikin, Liliana María Elena FinocchiaroAbstract:Suicide Gene Therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro
J. Andres Faiña Medín - One of the best experts on this subject based on the ideXlab platform.
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engineered human tmpk azt as a novel enzyme prodrug axis for Suicide Gene Therapy
Molecular Therapy, 2007Co-Authors: Takeya Sato, Anton Neschadim, J. Andres Faiña Medín, Manfred Konrad, Daniel H Fowler, Arnon LavieAbstract:See page 848 Gene Therapy and stem cell transplantation safety could be enhanced by control over the fate of therapeutic cells. Suicide Gene Therapy uses enzymes that convert prodrugs to cytotoxic entities; however, heterologous moieties with poor kinetics are employed. We describe a novel enzyme/prodrug combination for selectively inducing apoptosis in lentiviral vector–transduced cells. Rationally designed variants of human thymidylate kinase (tmpk) that effectively phosphorylate 3′-azido-3′-deoxythymidine (AZT) were efficiently delivered. Transduced Jurkat cell lines were eliminated by AZT. We demonstrate that this schema targeted both dividing and non-dividing cells, with a novel killing mechanism involving apoptosis induction via disruption of the mitochondrial inner membrane potential and activation of caspase-3. Primary murine and human T cells were also transduced and responded to AZT. Furthermore, low-dose AZT administration to non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice injected with transduced K562 cells suppressed tumor growth. This novel Suicide Gene Therapy approach can thus be integrated as a safety switch into therapeutic vectors.
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engineered human tmpk azt as a novel enzyme prodrug axis for Suicide Gene Therapy
Molecular Therapy, 2007Co-Authors: Takeya Sato, Anton Neschadim, J. Andres Faiña Medín, Manfred Konrad, Daniel H Fowler, Arnon LavieAbstract:Gene Therapy and stem cell transplantation safety could be enhanced by control over the fate of therapeutic cells. Suicide Gene Therapy uses enzymes that convert prodrugs to cytotoxic entities; however, heterologous moieties with poor kinetics are employed. We describe a novel enzyme/prodrug combination for selectively inducing apoptosis in lentiviral vector-transduced cells. Rationally designed variants of human thymidylate kinase (tmpk) that effectively phosphorylate 3'-azido-3'-deoxythymidine (AZT) were efficiently delivered. Transduced Jurkat cell lines were eliminated by AZT. We demonstrate that this schema targeted both dividing and non-dividing cells, with a novel killing mechanism involving apoptosis induction via disruption of the mitochondrial inner membrane potential and activation of caspase-3. Primary murine and human T cells were also transduced and responded to AZT. Furthermore, low-dose AZT administration to non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice injected with transduced K562 cells suppressed tumor growth. This novel Suicide Gene Therapy approach can thus be integrated as a safety switch into therapeutic vectors.
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Engineered human tmpk/AZT as a novel enzyme/prodrug axis for Suicide Gene Therapy.
Molecular therapy : the journal of the American Society of Gene Therapy, 2007Co-Authors: Takeya Sato, Anton Neschadim, Manfred Konrad, Daniel H Fowler, Arnon Lavie, J. Andres Faiña MedínAbstract:Gene Therapy and stem cell transplantation safety could be enhanced by control over the fate of therapeutic cells. Suicide Gene Therapy uses enzymes that convert prodrugs to cytotoxic entities; however, heterologous moieties with poor kinetics are employed. We describe a novel enzyme/prodrug combination for selectively inducing apoptosis in lentiviral vector-transduced cells. Rationally designed variants of human thymidylate kinase (tmpk) that effectively phosphorylate 3'-azido-3'-deoxythymidine (AZT) were efficiently delivered. Transduced Jurkat cell lines were eliminated by AZT. We demonstrate that this schema targeted both dividing and non-dividing cells, with a novel killing mechanism involving apoptosis induction via disruption of the mitochondrial inner membrane potential and activation of caspase-3. Primary murine and human T cells were also transduced and responded to AZT. Furthermore, low-dose AZT administration to non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice injected with transduced K562 cells suppressed tumor growth. This novel Suicide Gene Therapy approach can thus be integrated as a safety switch into therapeutic vectors.
Gerardo C. Glikin - One of the best experts on this subject based on the ideXlab platform.
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Cytokine-enhanced vaccine and Suicide Gene Therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
Cancer gene therapy, 2012Co-Authors: Liliana María Elena Finocchiaro, Gerardo C. GlikinAbstract:Cytokine-enhanced vaccine and Suicide Gene Therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
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Suicide Gene Therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro
Gene therapy, 2009Co-Authors: María L. Gil-cardeza, Marcela Solange Villaverde, Gabriel L. Fiszman, N A Altamirano, R A Cwirenbaum, Gerardo C. Glikin, Liliana María Elena FinocchiaroAbstract:Suicide Gene Therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro
Evren Alici - One of the best experts on this subject based on the ideXlab platform.
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Suicide Gene Therapy for graft-versus-host disease
Immunotherapy, 2010Co-Authors: Anna-maria Georgoudaki, Tolga Sutlu, Evren AliciAbstract:In alloGeneic hematopoietic stem cell transplantation, donor-derived T cells are key players for early immune reconstitution and efficient engraftment, as well as the graft-versus-leukemia and graft-versus-infection effects. However, a severe and quite common life-threatening complication is the development of graft-versus-host disease, during which the alloreactive donor T cells attack the host. Controlling graft-versus-host disease while preserving the benefits of graft-versus-leukemia still constitutes a challenge. A promising approach for the control of graft-versus-host disease is Suicide Gene Therapy, which involves the ex vivo Genetic modification of donor T cells with a Suicide Gene that allows for the selective elimination of the cells in vivo if graft-versus-host disease occurs. This article presents an overview of such approaches with special reference to lessons learned from previous clinical experiences, as well as a discussion of critical factors in Suicide Gene Therapy.
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TK.007: A novel, codon-optimized HSVtk(A168H) mutant for Suicide Gene Therapy.
Human gene therapy, 2010Co-Authors: Ellen Preuß, Evren Alici, Gösta Gahrton, Alexandra Treschow, Sebastian Newrzela, Daniela Brücher, Kristoffer Weber, Ulrika Felldin, Dorothee Von Laer, M. Sirac DilberAbstract:The authors Generate novel codon-optimized HSV thymidine kinase mutants that can be used for Suicide Gene Therapy applications. The efficacy of these novel variants was examined both in vitro and in vivo in an alloGeneic transplantation mouse model.
Boris Fehse - One of the best experts on this subject based on the ideXlab platform.
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Suicide Gene Therapy for the treatment of high-grade glioma: past lessons, present trends, and future prospects.
Neuro-oncology advances, 2020Co-Authors: Jubayer A Hossain, Boris Fehse, Antonio Marchini, Rolf Bjerkvig, Hrvoje MileticAbstract:Suicide Gene Therapy has represented an experimental cancer treatment modality for nearly 40 years. Among the various cancers experimentally treated by Suicide Gene Therapy, high-grade gliomas have been the most prominent both in preclinical and clinical settings. Failure of a number of promising Suicide Gene Therapy strategies in the clinic pointed toward a bleak future of this approach for the treatment of high-grade gliomas. Nevertheless, the development of new vectors and Suicide Genes, better prodrugs, more efficient delivery systems, and new combinatorial strategies represent active research areas that may eventually lead to better efficacy of Suicide Gene Therapy. These trends are evident by the current increasing focus on Suicide Gene Therapy for high-grade glioma treatment both in the laboratory and in the clinic. In this review, we give an overview of different Suicide Gene Therapy approaches for glioma treatment and discuss clinical trials, delivery issues, and immune responses.
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Cancer Suicide Gene Therapy with TK.007
Methods of Molecular Biology, 2018Co-Authors: Jubayer Al Hossain, Kristoffer Riecken, Hrvoje Miletic, Boris FehseAbstract:Cancer is a devastating disease characterized by uncontrolled and aggressive cell growth. Suicide Gene Therapy (SGT) facilitating induction of malignancy-specific cell death represents a novel therapeutic approach to treat cancer, which has been investigated in several cancer types with very promising results. In addition, SGT has been suggested as a safeguard in adoptive immunoTherapy and reGenerative-medicine settings. Generally, SGT consists of two steps-vector-mediated delivery of Suicide Genes into tumors and subsequent activation of the Suicide mechanism, e.g., by administration of a specific prodrug. This chapter provides a framework of protocols for basic and translational research using the Herpes-simplex-virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system, the most widely used Suicide Gene approach. The protocols provide standard guidelines for the preparation of high-titer third-Generation lentiviral vectors encoding a Genetically improved HSV-TK version known as TK.007 and its application in in vitro and in vivo treatment setups.
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475. Effects of HSV-Tk Mediated Suicide Gene Therapy on Normal Brain Cells
Molecular Therapy, 2016Co-Authors: Jubayer A Hossain, Kristoffer Riecken, Boris Fehse, Rolf Bjerkvig, Lars Romø Ystaas, Jelena Mrdalj, Kristjan Vaelk, Janne Grønli, Hrvoje MileticAbstract:Malignant gliomas, the largest group of primary intracerebral tumours, are one of the most difficult-to-cure cancers. For glioblastoma, the most malignant form of glioma, the median survival time is Generally less than one year. Lentiviral vector mediated Suicide Gene Therapy has been reported to be a potential therapeutic option for glioma and has been validated in clinically relevant animal models. At this end, specific targeting of tumor cells sparing normal brain tissue is a significant concern. Although several studies may suggest that HSV-Tk mediated Suicide Gene Therapy is not likely to be toxic for normal brain cells, it has never been investigated which effect lentiviral vector mediated HSV-Tk Suicide Gene Therapy exerts on the normal brain in a non-tumor setting. We addressed this important question by delivering the Suicide Gene HSV-Tk. 007 to the brain of healthy, immunocompetent rats using lentiviral vectors pseudotyped with VSV-G. First, we studied behavior patterns and assessed any potential neurological symptoms in treatment and the control groups, during prodrug treatment with Ganciclovir. We did not observe any significant changes in their physical and behavioral patterns. Then, we carried detailed histological/immunohistochemical analyses of the brains to analyze potential differences in the number of transduced brain cells between control and treatment groups. There was no significant difference in numbers of neurons, astrocytes and oligodendrocyte progenitor cells among the groups, indicating successful survival of these cells after pro-drug treatment. Furthermore, potential inflammation and apoptosis of brain cells were also investigated. No significant infiltration of immune cells was detected across the groups. We could not detect any sign of apoptosis or necrosis across all groups. In conclusion, our study which suggests that lentiviral Suicide Gene Therapy mediated by HSV-Tk. 007 is not toxic for normal brain cells.View Large Image | Download PowerPoint Slide
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tumor cells escape Suicide Gene Therapy by Genetic and epiGenetic instability
Blood, 2004Co-Authors: Oliver Frank, Christoph Heberlein, Cornelia Rudolph, Nils Von Neuhoff, Wolfram Ostertag, Boris Fehse, Axel Schambach, Evelin Schröck, Brigitte Schlegelberger, Carol StockingAbstract:Transfer and expression of Suicide Genes is one cornerstone of cancer Gene Therapy and is also considered as a proactive tool to enhance the safety of somatic transGenesis. Here we addressed whether retrovirus-mediated Suicide Gene Therapy would result in a predictable antitumor efficiency, given that problems related to Gene transfer are solved or that the Suicide Gene is used in a proactive approach. Using retroviral vectors encoding the thymidine kinase Gene of herpes simplex virus, we transduced EL-4 lymphoma cells and induced experimental tumors in conGeneic C57Bl/6 mice. Systemic administration of ganciclovir (GCV) resulted in remission of transduced clonal and polyclonal tumors in vivo. However, GCV-resistant relapses occurred and were found to be associated with postinsertional alterations of transGene structure or loss of the entire transGene. Complete loss of a retrovirally marked fusion chromosome was confirmed by spectral karyotyping. TransGene silencing occurred in another clone. We conclude that Genetic as well as epiGenetic instability related to biologic features of the tumor, the insertion site, and the vector represent relevant limitations of retroviral Suicide Gene Therapy. Considering the mechanisms of escape identified here, the proactive use of Suicide Genes to prevent complications of insertional mutaGenesis may still be efficient.
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Retroviral transduction of T lymphocytes for Suicide Gene Therapy in alloGeneic stem cell transplantation.
Bone Marrow Transplantation, 2000Co-Authors: Klaus Kühlcke, Francis Ayuk, C. Lindemann, Andrea Schilz, Ulrika M. Schade, Axel A. Fauser, Axel R. Zander, H.-g. Eckert, Boris FehseAbstract:Retroviral transduction of T lymphocytes for Suicide Gene Therapy in alloGeneic stem cell transplantation
