Gene Transfer of Suicide Genes for the Treatment of Malignant Gliomas: Efficacy, Limitations, and Perspectives for a Combined Immunotherapy

S. Benedetti, F. Di Meco, B. Pollo, M. G. Bruzzone, N. Cirenei, R. Spreafico, C. L. Solero, G. Broggi, St Di Donato, G. Finocchiaro

Research output: Contribution to journalArticle

Abstract

The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the "suicide gene" strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.

Original languageEnglish
JournalActa Neurochirurgica, Supplement
Volume1997
Issue number68
Publication statusPublished - 1997

Fingerprint

Glioma
Immunotherapy
Suicide
Genes
Prodrugs
Interleukin-4
Genetic Therapy
Therapeutics
Neoplasms
Ganciclovir
Thymidine Kinase
Simplexvirus
Nude Mice
Antineoplastic Agents
Cytokines
Growth

Keywords

  • Ganciclovir
  • Gene therapy
  • Interleukin-4
  • Malignant gliomas
  • Retrovirus
  • Suicide gene

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Neurology

Cite this

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title = "Gene Transfer of Suicide Genes for the Treatment of Malignant Gliomas: Efficacy, Limitations, and Perspectives for a Combined Immunotherapy",
abstract = "The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a {"}suicide gene{"} such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the {"}suicide gene{"} strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.",
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T2 - Efficacy, Limitations, and Perspectives for a Combined Immunotherapy

AU - Benedetti, S.

AU - Di Meco, F.

AU - Pollo, B.

AU - Bruzzone, M. G.

AU - Cirenei, N.

AU - Spreafico, R.

AU - Solero, C. L.

AU - Broggi, G.

AU - Di Donato, St

AU - Finocchiaro, G.

PY - 1997

Y1 - 1997

N2 - The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the "suicide gene" strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.

AB - The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the "suicide gene" strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.

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KW - Malignant gliomas

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KW - Suicide gene

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