Stereotactic Injection of Herpes Simplex Thymidine Kinase Vector Producer Cells (PA317-G1Tk1SvNa.7) and Intravenous Ganciclovir for the Treatment of Progressive or Recurrent Primary Supratentorial Pediatric Malignant Brain Tumors.

Larry E. Kun, Amar Gajjar, Michael Muhlbauer, Richard L. Heideman, Robert Sanford, Malcolm Brenner, Andrew Walter, James Langston, Jesse Jenkins, Sergio Facchini

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This study will evaluate the safety and efficacy of in vivo gene transfer of the herpes simplex thymidine kinase (HSV-Tk1) gene using PA317/G1Tk1SvNa.7 vector producer cells (VPC) in pediatric patients with progressive or recurrent primary supratentorial malignant brain tumors. Insertion of the HSV-Tk1 gene confers a sensitivity to the anti-herpes drug ganciclovir. It has been demonstrated that the direct injection of HSV-Tk vector producer cells into growing tumors in animals can result in their complete destruction with ganciclovir therapy. This selective destruction of growing tumors in situ is thought to result from the transfer of the HSV-Tk gene into the tumor cells and the production of toxic ganciclovir metabolites which result from the interaction of HSV-Tk and ganciclovir. This procedure can result in the cure of some experimental animals with limited systemic toxicity due to selective gene transfer into tumors. This clinical trial will focus on maximizing the relative number of vector producer cells to the tumor mass by stereotactically injecting VPCs into the tumor mass. Children with progressive or recurrent primary supratentorial malignant brain tumor which is accessible to stereotactic injection will be evaluated for the extent and location(s) of their disease before being entered into the study. Fifteen days after stereotactic injection of the tumor mass, ganciclovir will be administered at 5 mg/kg IV b.i.d. for 14 days. Upon completion of the treatment with HSV-Tk1 vector producer cells and ganciclovir, the patient will be followed monthly for the first three months, then every two months for the next twenty-one months, and annually for life thereafter.

Original languageEnglish (US)
Pages (from-to)1231-1255
Number of pages25
JournalHuman Gene Therapy
Issue number9
Publication statusPublished - Sep 1 1995


ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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