Related Experiment Video
Updated: Aug 21, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Endostatin gene therapy delivered by Salmonella choleraesuis in murine tumor models
Che-Hsin Lee1, Chao-Liang Wu, Ai-Li Shiau
1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Background:
Some anaerobic and facultatively anaerobic bacteria have been used experimentally as anticancer agents because of their selective growth in tumors. In this study, we exploited attenuated Salmonella choleraesuis as a tumoricidal agent and a vector to deliver the endostatin gene for tumor-targeted gene therapy.
Methods:
Attenuated S. choleraesuis carrying a eukaryotic expression plasmid encoding reporter gene was used to evaluate its abilities of tumor targeting and gene delivery in three syngeneic murine tumor models. Furthermore, S. choleraesuis carrying the endostatin expression vector was administered intraperitoneally into tumor-bearing mice, and its antitumor effect was evaluated.
Results:
Systemically administered S. choleraesuis preferentially accumulated within tumors for at least 10 days, forming tumor-to-normal tissue ratios exceeding 1000-10,000 : 1. Transgene expression via S. choleraesuis-mediated gene transfer also persisted for at least 10 days. Host immune responses and tumor hypoxia may influence tumor-targeting potential of S. choleraesuis. When systemically administered into mice bearing melanomas or bladder tumors, S. choleraesuis carrying the endostatin expression vector significantly inhibited tumor growth by 40-70% and prolonged survival of the mice. Furthermore, immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density, reduced expression of vascular endothelial growth factor (VEGF), and increased infiltration of CD8(+) T cells.
Conclusions:
These results suggest that tumor-targeted gene therapy using S. choleraesuis carrying the endostatin expression vector, which exerts tumoricidal and antiangiogenic activities, represents a promising strategy for the treatment of solid tumors.
Insights
Attenuated Salmonella choleraesuis bacteria were engineered to deliver the endostatin gene, effectively targeting tumors and inhibiting their growth. This novel approach shows promise for treating solid tumors through targeted gene therapy.
Area of Science:
- Oncology
- Microbiology
- Gene Therapy
Background:
- Anaerobic bacteria show selective tumor growth, making them potential anticancer agents.
- Attenuated Salmonella choleraesuis was investigated as a tumoricidal agent and gene delivery vector.
Purpose of the Study:
- To evaluate attenuated Salmonella choleraesuis for tumor targeting and gene delivery.
- To assess the antitumor effects of Salmonella choleraesuis carrying the endostatin gene.
Main Methods:
- Attenuated S. choleraesuis with an expression plasmid was tested in murine tumor models.
- Tumor-targeting, gene delivery, and antitumor efficacy of endostatin-expressing S. choleraesuis were evaluated.
Main Results:
- S. choleraesuis accumulated in tumors (>1000:1 ratio) and sustained transgene expression for over 10 days.
- Endostatin-expressing S. choleraesuis significantly inhibited melanoma and bladder tumor growth (40-70%) and prolonged survival.
- Tumor analysis revealed reduced microvessel density, decreased VEGF, and increased CD8(+) T cells.
Conclusions:
- Tumor-targeted gene therapy with endostatin-expressing S. choleraesuis is a promising strategy for solid tumor treatment.
- The approach demonstrates tumoricidal and antiangiogenic activities.
