Cancer Gene Therapy

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Georges Vassaux - One of the best experts on this subject based on the ideXlab platform.

  • herpes simplex virus thymidine kinase mediated suicide Gene Therapy using nano microbubbles and ultrasound
    Ultrasound in Medicine and Biology, 2008
    Co-Authors: Yukiko Watanabe, Georges Vassaux, Shiro Mori, Masahiko Takahashi, Tetsuya Kodama
    Abstract:

    Abstract A physical method using ultrasound (US) and nano/microbubbles (NBs) can deliver exogenous molecules noninvasively into a specific target site. In this study, we evaluated the application of this technology to Cancer Gene Therapy using prodrug activation Therapy. Low-intensity pulsed ultrasound (1 MHz; 1.3 W/cm2) and NBs were used to transduce the herpes simplex thymidine kinase (HSVtk) Gene in vitro, leading to Gene transfer. The addition of ganciclovir (GCV) to the transduced cells led to HSVtk/GCV-dependent cell death mediated by apoptosis. This technology was then assessed in vivo, using mice bearing subcutaneous tumors (1 MHz; 3.0 W/cm2). Gene transfer to the tumor, measured by luciferase activity, was transient, with a peak of expression 24 h after transduction, and decreased at 48 h, demonstrating the transient nature of US/NB-mediated Gene transfer. The therapeutic potential of this approach was evaluated through repeated intratumoral Gene delivery using US/NB-mediated transfer of the HSVtk Gene, followed by recurrent administration of GCV, using two different experimental treatment protocols. In both cases, dramatic reductions of the tumor size by a factor of four were observed. Altogether, these data demonstrate the potential of US/NB as a new physical Gene delivery method for Cancer Gene Therapy. (E-mail: kodama@tubero.tohoku.ac.jp )

  • use of suicide Genes for Cancer Gene Therapy study of the different approaches
    Expert Opinion on Biological Therapy, 2004
    Co-Authors: Georges Vassaux, Pilar Martinduque
    Abstract:

    Cancer is a disease of high incidence for which conventional treatments are not necessarily effective. There is a need for the development of new alternative strategies. Among them, suicide Gene Therapy has been developed. In this approach, a Gene encoding for a protein toxic under particular conditions is delivered to the target cells, resulting in their death. Although this approach has been in development for a long time, new combinations with other Gene Therapy areas, such as selective replicative viruses, tumour targeting, or conventional treatments such as chemo- or radioTherapy, are currently being tested. This review will summarise some of these approaches.

Tetsuya Kodama - One of the best experts on this subject based on the ideXlab platform.

  • herpes simplex virus thymidine kinase mediated suicide Gene Therapy using nano microbubbles and ultrasound
    Ultrasound in Medicine and Biology, 2008
    Co-Authors: Yukiko Watanabe, Georges Vassaux, Shiro Mori, Masahiko Takahashi, Tetsuya Kodama
    Abstract:

    Abstract A physical method using ultrasound (US) and nano/microbubbles (NBs) can deliver exogenous molecules noninvasively into a specific target site. In this study, we evaluated the application of this technology to Cancer Gene Therapy using prodrug activation Therapy. Low-intensity pulsed ultrasound (1 MHz; 1.3 W/cm2) and NBs were used to transduce the herpes simplex thymidine kinase (HSVtk) Gene in vitro, leading to Gene transfer. The addition of ganciclovir (GCV) to the transduced cells led to HSVtk/GCV-dependent cell death mediated by apoptosis. This technology was then assessed in vivo, using mice bearing subcutaneous tumors (1 MHz; 3.0 W/cm2). Gene transfer to the tumor, measured by luciferase activity, was transient, with a peak of expression 24 h after transduction, and decreased at 48 h, demonstrating the transient nature of US/NB-mediated Gene transfer. The therapeutic potential of this approach was evaluated through repeated intratumoral Gene delivery using US/NB-mediated transfer of the HSVtk Gene, followed by recurrent administration of GCV, using two different experimental treatment protocols. In both cases, dramatic reductions of the tumor size by a factor of four were observed. Altogether, these data demonstrate the potential of US/NB as a new physical Gene delivery method for Cancer Gene Therapy. (E-mail: kodama@tubero.tohoku.ac.jp )

Pilar Martinduque - One of the best experts on this subject based on the ideXlab platform.

  • use of suicide Genes for Cancer Gene Therapy study of the different approaches
    Expert Opinion on Biological Therapy, 2004
    Co-Authors: Georges Vassaux, Pilar Martinduque
    Abstract:

    Cancer is a disease of high incidence for which conventional treatments are not necessarily effective. There is a need for the development of new alternative strategies. Among them, suicide Gene Therapy has been developed. In this approach, a Gene encoding for a protein toxic under particular conditions is delivered to the target cells, resulting in their death. Although this approach has been in development for a long time, new combinations with other Gene Therapy areas, such as selective replicative viruses, tumour targeting, or conventional treatments such as chemo- or radioTherapy, are currently being tested. This review will summarise some of these approaches.

James S Economou - One of the best experts on this subject based on the ideXlab platform.

  • in vivo Cancer Gene Therapy with a recombinant interleukin 2 adenovirus vector
    Cancer Gene Therapy, 1996
    Co-Authors: Eric M Toloza, Kelly K Hunt, Stephen G Swisher, William H Mcbride, Shen Pang, K Rhoades, T Drake, Arie S Belldegrun, John A Glaspy, James S Economou
    Abstract:

    Abstract Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo Gene delivery. In vivo Therapy of established murine fibrosarcoma and mammary carcinomas was attempted with intratumoral injections of a recombinant AdV vector in which the human interleukin-2 (IL-2) Gene was driven by the cytomegalovirus enhancer/promoter. Delayed growth and rejection of some tumors could be achieved with a cumulative virus dose of 2 to 6 x 10(9) plaque-forming units in two or three divided doses. Lower viral doses were ineffective, and higher doses resulted in animal death due to IL-2 toxicity. Using AdV vectors with the marker Genes beta-galactosidase and luciferase, it is clear that even small volume (10 to 20 microL) intratumoral injections result in substantial systemic delivery of a portion of the virus dose. These findings define the potential and limitations of in vivo AdV-based Cancer Gene Therapy and provide support for strategies to develop tumor-specific vectors.

Gao Bao-mei - One of the best experts on this subject based on the ideXlab platform.

  • The Hammerhead Ribozyme Mediated Repression of VEGF for Cancer Gene Therapy
    Chinese Journal of Cancer, 2005
    Co-Authors: Gao Bao-mei
    Abstract:

    Objective: To establish a novel and robust hammerhead ribozyme system against the Vascular Endothelial Growth Factor (VEGF) for anti-Cancer Gene Therapy. Methods: The structural analysis of the 2ndstructure of the VEGF RNA and the vector construction of hammerhead ribozymes ( 1 -4) against VEGF leader region( +1 to +75) ; The in vitro analyses of ribozyme mediated specific cleavage; The in cell evaluation of the ribozyme mediated cleavage of the VEGF RNA. Results: Ribozymes targeting +8, +36, or +71 (Rzl,3 and 4) of the exposed region or +17 (Rz2) of the un exposed region of VEGF RNA were constructed in pGVal and pFB retroviral vector systems; Rzl ,3 and 4, but not Rz2, specifically cleaved the VEGF RNA and brought the VEGF RNA level down to 61. 7% , 27. 6% and 44. 8% (luciferase activity ) as well as 66. 3% , 27. 0% and 30.0% ( protein level) of the control; The same set of ribozymes reduced the co-transfected VEGF-LUC RNA level down to 81.4% ,56. 6% and 69. 1% of the control in a transient transfection analysis and essentially abolished the endogenous VEGF RNA in the stable transfected setting. Conclusion: We have established three effective hammerhead ribozyme vector systems targeting +8, +36 and +71 of the VEGF RNA.