Bystander-Mediated Regression of Murine Neuroblastoma via Retroviral Transfer of the HSV-TK Gene.
10.3346/jkms.2004.19.1.107
- Author:
Hyun Sang CHO
1
;
Hye Ran LEE
;
Moon Kyu KIM
Author Information
1. Department of Pediatrics, Hallym University College of Medicine, Seoul, Korea. mkkim@sunlin.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Bystander Effect;
Neuroblastoma;
Gene Therapy
- MeSH:
Animals;
Apoptosis;
Bystander Effect;
CD4-Positive T-Lymphocytes/metabolism;
CD8-Positive T-Lymphocytes/metabolism;
Cell Line, Tumor;
Connexin 43/biosynthesis;
Gap Junctions;
Gene Therapy/*methods;
*Gene Transfer Techniques;
Human;
Immunohistochemistry;
Mice;
Neoplasm Transplantation;
Neuroblastoma/*therapy;
Phosphorylation;
Retroviridae/genetics;
Simplexvirus/*enzymology;
Support, Non-U.S. Gov't;
Thymidine Kinase/*genetics;
Time Factors
- From:Journal of Korean Medical Science
2004;19(1):107-112
- CountryRepublic of Korea
- Language:English
-
Abstract:
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirusmediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
