IL-18-producing Salmonella inhibit tumor growth
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Updated: Jul 3, 2026
Measuring Growth and Gene Expression Dynamics of Tumor-Targeted S. Typhimurium Bacteria
Published on: July 6, 2013
M Loeffler1, G Le'Negrate, M Krajewska
1Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Abstract:
Previous studies have shown that intravenously applied bacteria can accumulate in tumors and lead to sporadic tumor regression. Recently, systemic administration of attenuated Salmonella typhimurium was demonstrated to generate no significant side effects in humans, but also no antitumor responses. We report the enhanced antitumor activity in preclinical mouse cancer models of nonvirulent S. typhimurium engineered to synthesize the cytokine Interleukin-18 (IL-18). IL-18-producing bacteria (but not control bacteria) inhibit the growth of primary subcutaneous tumors as well as pulmonary metastases in immunocompetent mice challenged with syngeneic multidrug-resistant clones of murine carcinoma cell lines, without overt toxicity to normal tissues. Antitumor activity was associated with increased accumulation of T-lymphocytes and NK cells in tumors, and massive infiltration of granulocytes, as well as increased intra-tumoral production of several cytokines. In summary, these findings provide evidence of promising preclinical antitumor activity of IL-18-expressing, attenuated S. typhimurium, suggesting a novel strategy for cancer immunotherapy.
Insights
Engineered bacteria producing Interleukin-18 (IL-18) showed enhanced antitumor activity in mouse cancer models. This novel cancer immunotherapy strategy effectively inhibited tumor growth and metastases with minimal toxicity.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- Intravenously administered bacteria can accumulate in tumors, potentially causing tumor regression.
- Attenuated Salmonella typhimurium has shown a good safety profile in humans but lacked antitumor responses.
Purpose of the Study:
- To evaluate the enhanced antitumor activity of nonvirulent Salmonella typhimurium engineered to synthesize Interleukin-18 (IL-18).
- To assess the safety and efficacy of this novel cancer immunotherapy in preclinical mouse models.
Main Methods:
- Engineering nonvirulent S. typhimurium to produce IL-18.
- Challenging immunocompetent mice with syngeneic multidrug-resistant murine carcinoma cell lines.
- Administering IL-18-producing bacteria or control bacteria systemically.
Main Results:
- IL-18-producing bacteria significantly inhibited primary tumor growth and pulmonary metastases.
- Antitumor activity was linked to increased T-lymphocyte and NK cell accumulation in tumors.
- Massive granulocyte infiltration and increased intra-tumoral cytokine production were observed without overt toxicity.
Conclusions:
- Engineered, attenuated S. typhimurium expressing IL-18 demonstrates promising preclinical antitumor activity.
- This approach represents a novel strategy for developing effective cancer immunotherapies.
- Further research is warranted to explore the clinical potential of IL-18-expressing bacteria.
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