Investigation for safe and efficient gene therapy for glioblastomas using radiation inducible promoters.

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nagasaki University
• Principal Investigator: TOKUNAGA Yoshiharu Nagasaki University Hospital, Lecturer, 医学部附属病院, 講師 (00207557)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA Shunich Nagasaki University School of Medicine, Professor, 医学部, 教授 (30200679) ; IZUMO Tsuyoshi Nagasaki University Hospital, Assistant, 医学部附属病院, 助手 (40343347) ; OHTSURU Akira Nagasaki University School of Medicine, Assistant, 医学部, 助手 (00233198)
• Project Period (FY): 2001 – 2002
• Keywords: gliobastoma / radiation / suicide gene therapy / cre-loxP / HSV-TK / radiation inducible

Research Abstract

Tissue- or tumor-specific promoters offer a promising approach to the selective targeting of cancer gene therapy because such promoters are able to express a target gene in a cell-type specific manner. However, the activity of cell-type specific promoter is generally low, being the limitation of clinical usefulness for molecular tumor targeting. To, therefore, establish radiation inducible tumor cell-specific gene therapy for glioblastomas, we developed cre-loxP based vector system. The cre vector harbors Egr-1 promoter and cre gene, which transcriptant splices the loxP site of the other vector, which harbors the loxP gene, and this vector expresses herpes simplex virus thymidine kinase (HSV-TK) gene driven by CMV promoter.
To date, we could reach significant results neither in vitro gene therapy nor in vivo experiment. We think these results were due to complexity of this cre-loxP system, using two identical vector systems.
So, we are now investigating more effective gene therapy system, using simple vector system driven by the radiation inducible Egr-1 promoter.