A Study of the Bystander Effect and Its Enhancement in HSV-TK Gene Therapy Using a Murine Neuroblastoma Model.
- Author:
Hyun Sang CHO
1
;
Moon Kyu KIM
;
Chong Young PARK
Author Information
1. Department of Pediatrics, College of Medicine, Hallym University, Seoul, Korea. shcoh@hallym@or.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
HSV-TK;
Bystander effect;
Neuroblastoma
- MeSH:
Animals;
Antibodies, Monoclonal;
Bystander Effect*;
Connexin 43;
Gap Junctions;
Genetic Therapy*;
Immunohistochemistry;
Mice;
Neuroblastoma*;
Simplexvirus;
Thymidine
- From:Journal of the Korean Pediatric Society
2002;45(3):354-361
- CountryRepublic of Korea
- Language:Korean
-
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.
