Journal of the Korean Pediatric Society 2002;45(3):354-361.
Published online March 15, 2002.
A Study of the Bystander Effect and Its Enhancement in HSV-TK Gene Therapy Using a Murine Neuroblastoma Model
Hyun Sang Cho1, Moon Kyu Kim2, Chong Young Park2
1Department of Pediatrics, College of Medicine, Hallym University, Seoul, Korea
2Department of Pediatrics, College of Medicine, Ajou University, Suwon, Korea
마우스 신경모세포종 모델을 이용한 HSV-TK 유전자치료에서 Bystander 효과 및 증폭에 관한 연구
조현상1, 김문규2, 박종명2
1한림대학교 의과대학 소아과학교실
2아주대학교 의과대학 소아과학교실
Correspondence: 
Hyun Sang Cho, Email: hscho@hallym.or.kr
Abstract
Purpose
: Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma.
Methods
: To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect.
Results
: A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model.
Conclusion
: We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.
Key Words: HSV-TK, Bystander effect, Neuroblastoma


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