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Updated: May 2, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Systemic administration of attenuated Salmonella typhimurium in combination with interleukin-21 for cancer therapy
Yuxuan Wang1, Jianxiang Chen1, Bo Tang2
1The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093;
Abstract:
Attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 has been employed as a powerful anticancer agent due to its selective accumulation in tumors for targeted therapy. S. typhimurium has been demonstrated to constitute a delivery tool carrying antiangiogenic or proapoptotic genes that treat cancer. The hydrodynamic tail vein (HTV) injection of naked plasmid DNA has been developed as an effective gene delivery strategy, which has been successfully used in vivo. The aim of this study was to develop a combination therapy of S. typhimurium VNP20009 and HTV injection of interleukin-21 (IL-21) expression plasmid to evaluate the antitumor potential on an experimental melanoma model. Consistent with previous results, single VNP20009 treatment was demonstrated to possess effective activities to suppress tumor growth and prolong animal survival. Moreover, HTV injection of IL-21 plasmid promoted the antitumor activities of VNP20009. The mice that were administered combined therapy exhibited smaller tumor sizes and longer survival time compared with those administered VNP20009 or IL-21 treatment alone. IL-21 induced more infiltrating natural killer (NK) and T cells to the tumor area. These findings indicated that S. typhimurium in combination with IL-21 promotes antitumor immune responses, suggesting a novel strategy in the treatment of cancer.
Insights
Attenuated Salmonella typhimurium (S. typhimurium) VNP20009 combined with interleukin-21 (IL-21) gene therapy effectively suppressed melanoma tumor growth. This novel combination enhanced antitumor immune responses, leading to longer survival in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 selectively targets tumors for cancer therapy.
- S. typhimurium can be engineered to deliver therapeutic genes, such as antiangiogenic or proapoptotic agents.
- Hydrodynamic tail vein (HTV) injection is an established in vivo gene delivery method for plasmid DNA.
Purpose of the Study:
- To evaluate the combined antitumor potential of S. typhimurium VNP20009 and HTV injection of interleukin-21 (IL-21) expression plasmid.
- To assess the efficacy of this combination therapy on an experimental melanoma model.
- To investigate the impact of combination therapy on immune cell infiltration in the tumor microenvironment.
Main Methods:
- Utilized an experimental melanoma model in mice.
- Administered S. typhimurium VNP20009 alone and in combination with HTV injection of IL-21 plasmid.
- Monitored tumor growth, animal survival, and immune cell infiltration (NK and T cells).
Main Results:
- Single VNP20009 treatment suppressed tumor growth and prolonged survival.
- Combination therapy significantly reduced tumor size and extended survival compared to single treatments.
- IL-21 gene therapy enhanced the antitumor effects of VNP20009 by increasing NK and T cell infiltration into tumors.
Conclusions:
- Combination therapy of S. typhimurium VNP20009 and IL-21 gene delivery demonstrates potent antitumor activity.
- This combination strategy effectively promotes antitumor immune responses.
- The findings suggest a promising novel therapeutic approach for cancer treatment.
