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

doi:10.1038/sj.gt.3300379

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 journal › Article › peer-review

139 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 language	English
Pages (from-to)	244-251
Number of pages	8
Journal	Gene Therapy
Volume	4
Issue number	3
DOIs	https://doi.org/10.1038/sj.gt.3300379
State	Published - 1 Jan 1997
Externally published	Yes

Keywords

Bystander effect
Cancer
Ganciclovir
Gene therapy
Suicide gene
Thymidine kinase

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.gt.3300379

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

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.",

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author = "H. Ishii-Morita and R. Agbaria and Mullen, {C. A.} and H. Hirano and Koeplin, {D. A.} and Z. Ram and Oldfield, {E. H.} and Johns, {D. G.} and Blaese, {R. M.}",

year = "1997",

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doi = "10.1038/sj.gt.3300379",

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AU - Ishii-Morita, H.

AU - Agbaria, R.

AU - Mullen, C. A.

AU - Hirano, H.

AU - Koeplin, D. A.

AU - Ram, Z.

AU - Oldfield, E. H.

AU - Johns, D. G.

AU - Blaese, R. M.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - '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.

AB - '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.

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KW - Cancer

KW - Ganciclovir

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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