Mechanism of 'bystander effect' killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment

H. Ishii-Morita, R. Agbaria, C. A. Mullen, H. Hirano, D. A. Koeplin, Z. Ram, E. H. Oldfield, D. G. Johns, R. M. Blaese

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

'Bystander' killing of adjacent wild-type tumor cells was seen when tumors transduced with the herpes thymidine kinase gene were treated with the antiviral agent ganciclovir (GCV). Some tumors were 'bystander-sensitive' while others were 'bystander-resistant'. Mixtures of different 'sensitive' tumor lines showed cross-transfer of bystander killing, while in mixtures of 'resistant' with 'sensitive' tumors the resistant phenotype was predominant. Using 3H-GCV 'sensitive' mixtures, phosphorylated 3H-GCV was found in both herpes thymidine kinase transduced and unmodified cells, while 'resistant' cell combinations showed little or no transfer of phosphorylated GCV between cells. The capacity of intracellularly produced nucleotide toxin to spread from cell to cell within a tumor mass effectively amplifies the apparent efficiency of gene transfer in the tumor and makes feasible the use of this system for therapy of localized cancer.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalGene Therapy
Volume4
Issue number3
DOIs
StatePublished - 1 Jan 1997
Externally publishedYes

Keywords

  • Bystander effect
  • Cancer
  • Ganciclovir
  • Gene therapy
  • Suicide gene
  • Thymidine kinase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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