EFFECT OF HERPES-SIMPLEX VIRUS THYMIDINE KINASE EXPRESSION LEVELS ON GANCICLOVIR-MEDIATED CYTOTOXICITY AND THE BESTANDER EFFECT

被引：94

作者：

CHEN, CY ^{[1
]}

CHANG, YN ^{[1
]}

RYAN, P ^{[1
]}

LINSCOTT, M ^{[1
]}

MCGARRITY, GJ ^{[1
]}

CHIANG, YL ^{[1
]}

机构：

[1] GENET THERAPY INC, GAITHERSBURG, MD 20878 USA

来源：

HUMAN GENE THERAPY | 1995年 / 6卷 / 11期

关键词：

D O I：

10.1089/hum.1995.6.11-1467

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Transfer of the herpes simplex virus type-1 thymidine kinase (HSV-tk) gene into tumor cells followed by ganciclovir (GCV) administration, will provide selective tumor cell killing. We studied the effect of herpes simplex virus thymidine kinase (HSV-tk) expression level on the HSV-tk/GCV-mediated ''bystander effect.'' Clones of HSV-tk-transduced rat glioma cells (9L) were isolated that stably expressed with different levels of HSV-tk, All clones studied had similar sensitivity to ganciclovir with IC50 values ranging from 0.45 to 1.3 mu M. Within certain enzyme level thresholds, in vitro evaluation of the bystander effect has shown that clones with higher level of HSV-tk expression exhibited a better bystander effect. Interestingly, the bystander effect was observed between different cell types, Both the transduction efficiency and bystander effect are essential factors for the success of the antitumor effect by the HSV-tk/prodrug GCV suicide gene system.

引用

页码：1467 / 1476

页数：10

共 35 条

[1] ALLEY MC, 1988, CANCER RES, V48, P589
[2] THYMIDINE KINASE-MEDIATED KILLING OF RAT-BRAIN TUMORS
BARBA, D
HARDIN, J
RAY, J
GAGE, FH
[J]. JOURNAL OF NEUROSURGERY, 1993, 79 (05) : 729 - 735
[3] DEVELOPMENT OF ANTITUMOR IMMUNITY FOLLOWING THYMIDINE KINASE-MEDIATED KILLING OF EXPERIMENTAL BRAIN-TUMORS
BARBA, D
HARDIN, J
SADELAIN, M
GAGE, FH
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (10) : 4348 - 4352
[4] IN-VITRO EVIDENCE THAT METABOLIC COOPERATION IS RESPONSIBLE FOR THE BYSTANDER EFFECT OBSERVED WITH HSV TK RETROVIRAL GENE-THERAPY
BI, WL
PARYSEK, LM
WARNICK, R
STAMBROOK, PJ
[J]. HUMAN GENE THERAPY, 1993, 4 (06) : 725 - 731
[5] BOVIATSIS EJ, 1994, CANCER RES, V54, P5745
[6] REGRESSION OF ESTABLISHED MACROSCOPIC LIVER METASTASES AFTER IN-SITU TRANSDUCTION OF A SUICIDE GENE
CARUSO, M
PANIS, Y
GAGANDEEP, S
HOUSSIN, D
SALZMANN, JL
KLATZMANN, D
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) : 7024 - 7028
[7] CHEN CA, 1988, BIOTECHNIQUES, V6, P632
[8] GENE-THERAPY FOR BRAIN-TUMORS - REGRESSION OF EXPERIMENTAL GLIOMAS BY ADENOVIRUS-MEDIATED GENE-TRANSFER IN-VIVO
CHEN, SH
SHINE, HD
GOODMAN, JC
GROSSMAN, RG
WOO, SLC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) : 3054 - 3057
[9] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[10] INVIVO GENE-TRANSFER WITH RETROVIRAL VECTOR PRODUCER CELLS FOR TREATMENT OF EXPERIMENTAL BRAIN-TUMORS
CULVER, KW
RAM, Z
WALLBRIDGE, S
ISHII, H
OLDFIELD, EH
BLAESE, RM
[J]. SCIENCE, 1992, 256 (5063) : 1550 - 1552

← 1 2 3 4 →