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

被引：0

作者：

H Ishii-Morita

R Agbaria

CA Mullen

H Hirano

DA Koeplin

Z Ram

EH Oldfield

DG Johns

RM Blaese

机构：

[1] Clinical Gene Therapy Branch,

[2] National Center for Human Genome Research,undefined

[3] Laboratory of Medicinal Chemistry,undefined

[4] National Cancer Institute,undefined

[5] Experimental Immunology Branch,undefined

[6] National Cancer Institute,undefined

[7] Howard Hughes Medical Research Institute Scholars Program,undefined

[8] Surgical Neurology Branch,undefined

[9] National Institute of Neurologic Disorders and Stroke,undefined

[10] National Institutes of Health,undefined

来源：

Gene Therapy | 1997年 / 4卷

关键词：

thymidine kinase; suicide gene; bystander effect; ganciclovir; cancer; gene therapy;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

‘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 with ‘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.

引用

页码：244 / 251

页数：7