J Korean Pediatr Soc.  2002 Mar;45(3):354-361.

A Study of the Bystander Effect and Its Enhancement in HSV-TK Gene Therapy Using a Murine Neuroblastoma Model

• Cho HS
• Kim MK
• Park CY

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.

Keyword

HSV-TK; Bystander effect; Neuroblastoma

MeSH Terms

Animals
Antibodies, Monoclonal
Bystander Effect*
Connexin 43
Gap Junctions
Genetic Therapy*
Immunohistochemistry
Mice
Neuroblastoma*
Simplexvirus
Thymidine
Antibodies, Monoclonal
Connexin 43
Thymidine