J Korean Pediatr Soc.  2001 Nov;44(11):1249-1253.

Bystander Effect of HSV-TK/GCV Gene Therapy in Murine Neuroblastoma

• Shim EJ
• Kim SR
• Park EH
• Cho HS
• Cha JK
• Lee HR

Abstract

PURPOSE: To demonstrate the bystander effect in murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo.
METHODS
The LNC/TK vector was transfered in vitro into the neuro-2a cells, murine neuroblastoma cell line. Variable mixed populations of neuro-2a cells consisting of HSV-TK+ or HSV-TK- were plated into culture plates and treated with GCV for another 4 days. Surviving cells were counted and cell viability was determinated. For investigating the in vivo bystander effect, variable mixed populations of neuro-2a cells consisting of HSV-TK+ and HSV-TK- were inoculated into A/J mice. The tumor size was measured following injection of GCV for 7 days.
RESULTS
The survival rate of the 100% neuro-2a/TK group was 90%, 25%, 5% and 0%, of 50% neuro-2a/TK group was 92%, 30%, 10% and 0%, and of the 10% neuro-2a/TK group was 95%, 40%, 15% and 5%. But, the survival rate of 0% neuro-2a/TK group was 120%, 150%, 180% and 220% on days 1, 2, 3, and 4 respectively. In the 100% and 50% neuro-2a/TK groups, tumor had disappeared following administration of GCV and in 10% neuro-2a/TK group, tumor size was not increased during GCV treatment. In 0% neuro-2a/TK group, tumor size increased during administration of GCV and all mice died after 6 weeks.
CONCLUSIONS
We demonstrated the bystander effect in a murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo. These results suggest that HSV-TK/GCV gene therapy may be useful for treatment of neuroblastoma.

Keyword

Bystander effect; HSV-TK; Neuroblastoma

MeSH Terms

Animals
Bystander Effect*
Cell Line
Cell Survival
Genetic Therapy*
Mice
Neuroblastoma*
Survival Rate