All issues > Volume 45(3); 2002

Original Article

J Korean Pediatr Soc. 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 HS Cho¹, Moon Kyu MK Kim², Chong Young CY Park²

¹Department of Pediatrics, College of Medicine, Hallym University, Seoul, Korea
²Department of Pediatrics, College of Medicine, Ajou University, Suwon, Korea

Correspondence Hyun Sang HS 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.

Keywords :HSV-TK, Bystander effect, Neuroblastoma