PRELIMINARY IN-VITRO EFFICACY AND TOXICITIES STUDIES OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE SYSTEM FOR THE TREATMENT OF BREAST-CANCER

被引:16
作者
LINK, CJ
KOLB, EM
MULDOON, RR
机构
来源
HYBRIDOMA | 1995年 / 14卷 / 02期
关键词
D O I
10.1089/hyb.1995.14.143
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A novel gene therapy strategy is the use of suicide genes that transfer a drug sensitivity to cancer cells, We present preliminary in vitro efficacy data and in vivo toxicity data using the herpes simplex thymidine kinase (HStk) gene for breast cancer, The long-term objective of this project is to develop novel approaches for the treatment of breast cancer using in vivo retroviral gene transfer, Intraductal breast cancer cell line HTB126 transduced by an HStk retroviral vector is efficiently inhibited in vitro after GCV exposure, Further analysis revealed a bystander effect through which nontransduced HTB126 cells were also inhibited by GCV when cocultured with HStk-transduced HTB126 cells, In cell mixture experiments if only 1% of the cells in culture contained the HStk gene, 83% of the culture could be destroyed, Next safety studies were performed, Vector producer cells (VPC) were implanted into the mammary fat pads of athymic nude mice, The mice were then treated with GCV and monitored for regression of the VPC, The injected VPC regressed rapidly in response to the GCV therapy and produced no evidence of local or systemic toxicity in the animals, These in vitro efficacy data and in vivo toxicity studies lend support to the further development of an in vivo therapy model to treat breast cancer.
引用
收藏
页码:143 / 147
页数:5
相关论文
共 20 条
[1]   IN-VITRO EVIDENCE THAT METABOLIC COOPERATION IS RESPONSIBLE FOR THE BYSTANDER EFFECT OBSERVED WITH HSV TK RETROVIRAL GENE-THERAPY [J].
BI, WL ;
PARYSEK, LM ;
WARNICK, R ;
STAMBROOK, PJ .
HUMAN GENE THERAPY, 1993, 4 (06) :725-731
[2]   REGRESSION OF ESTABLISHED MACROSCOPIC LIVER METASTASES AFTER IN-SITU TRANSDUCTION OF A SUICIDE GENE [J].
CARUSO, M ;
PANIS, Y ;
GAGANDEEP, S ;
HOUSSIN, D ;
SALZMANN, JL ;
KLATZMANN, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) :7024-7028
[3]   INVIVO GENE-TRANSFER WITH RETROVIRAL VECTOR PRODUCER CELLS FOR TREATMENT OF EXPERIMENTAL BRAIN-TUMORS [J].
CULVER, KW ;
RAM, Z ;
WALLBRIDGE, S ;
ISHII, H ;
OLDFIELD, EH ;
BLAESE, RM .
SCIENCE, 1992, 256 (5063) :1550-1552
[4]   GENE-THERAPY FOR THE TREATMENT OF MALIGNANT BRAIN-TUMORS WITH IN-VIVO TUMOR TRANSDUCTION WITH THE HERPES-SIMPLEX THYMIDINE KINASE GENE GANCICLOVIR SYSTEM [J].
CULVER, KW ;
VANGILDER, J ;
LINK, CJ ;
CARLSTROM, T ;
BUROKER, T ;
YUH, W ;
KOCH, K ;
SCHABOLD, K ;
DOORNBAS, S ;
WETJEN, B ;
BLAESE, RM .
HUMAN GENE THERAPY, 1994, 5 (03) :343-379
[5]   PLASMID-DETERMINED RESISTANCE TO ANTI-MICROBIAL AGENTS [J].
DAVIES, J ;
SMITH, DI .
ANNUAL REVIEW OF MICROBIOLOGY, 1978, 32 :469-518
[6]  
EZZIDINE ZD, 1991, NEW BIOL, V3, P608
[7]  
FREEMAN SM, 1993, CANCER RES, V53, P5274
[8]  
Freeman SM, 1992, HUM GENE THER, V3, P342
[9]   THYMIDINE KINASE OBLITERATION - CREATION OF TRANSGENIC MICE WITH CONTROLLED IMMUNE-DEFICIENCY [J].
HEYMAN, RA ;
BORRELLI, E ;
LESLEY, J ;
ANDERSON, D ;
RICHMAN, DD ;
BAIRD, SM ;
HYMAN, R ;
EVANS, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2698-2702
[10]  
ISHII H, 1994, J CELL BIOCHEM, V18, P226