Efficacy of lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer.
Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive, HIV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK, followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006).


CONCLUSIONS
Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.
Kong
Beihua
B
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China. kongbeihua@yahoo.com.cn
Wang
Wenxia
W
Liu
Chunsheng
C
Song
Li
L
Ma
Daoxin
D
Qu
Xun
X
Jiang
Jie
J
Yang
Xingsheng
X
Zhang
Youzhong
Y
Wang
Bo
B
Wei
Ming Q
MQ
Yang
Qifeng
Q
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D013937:Thymidine Kinase