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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
Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth
Markus Loeffler1, Gaelle Le'Negrate, Maryla Krajewska
1Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Intravenously-applied bacteria tend to accumulate in tumors and can sporadically lead to tumor regression. Systemic administration of attenuated Salmonella typhimurium is safe and has shown no significant adverse effects in humans. The purpose of this study was to test the hypothesis that engineering S. typhimurium to express a chemokine, CCL21, would increase anti-tumor activity. We engineered an attenuated strain of S. typhimurium to produce the chemokine CCL21. Attenuated S. typhimurium expressing CCL21 significantly inhibited the growth of primary tumors and pulmonary metastases in preclinical models of multi-drug-resistant murine carcinomas, while control bacteria did not. Histological analysis of tumors showed marked inflammatory cell infiltrates in mice treated with CCL21-expressing but not control bacteria. Levels of cytokines and chemokines known to be induced by CCL21 [e.g., interferon-gamma (INFgamma), CXCL9, and CXCL10] were significantly elevated in tumors of mice treated with CCL21-expressing but not control S. typhimurium. The anti-tumor activity was found to be dependent on CD4- and CD8-expressing cells, based on antibody-mediated in vivo immuno-depletion experiments. Anti-tumor activity was achieved without evidence of toxicity. In summary, chemokine-expressing, attenuated bacteria may provide a novel approach to cancer immunotherapy for effective and well-tolerated in vivo delivery of immunomodulatory proteins.
Insights
Engineered Salmonella typhimurium bacteria expressing CCL21 demonstrated significant anti-tumor activity in preclinical models. This novel cancer immunotherapy approach enhanced immune cell infiltration and cytokine production without toxicity.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Intravenously administered bacteria accumulate in tumors, potentially inducing regression.
- Attenuated Salmonella typhimurium is safe for systemic use in humans.
- Chemokines can modulate immune responses against tumors.
Purpose of the Study:
- To engineer attenuated Salmonella typhimurium to express the chemokine CCL21.
- To evaluate the anti-tumor efficacy of engineered S. typhimurium.
- To assess the safety and immunomodulatory effects of CCL21-expressing bacteria.
Main Methods:
- Engineered an attenuated S. typhimurium strain to produce CCL21.
- Tested efficacy in preclinical models of multi-drug-resistant murine carcinomas.
- Analyzed tumor histology, cytokine/chemokine levels, and immune cell populations (CD4+, CD8+).
Main Results:
- CCL21-expressing S. typhimurium significantly inhibited primary tumor and pulmonary metastasis growth.
- Treated tumors showed increased inflammatory cell infiltrates and elevated CCL21-induced cytokines (INFgamma, CXCL9, CXCL10).
- Anti-tumor activity was dependent on CD4+ and CD8+ T cells and showed no toxicity.
Conclusions:
- Engineered, attenuated bacteria expressing CCL21 offer a novel cancer immunotherapy strategy.
- This approach facilitates effective in vivo delivery of immunomodulatory proteins.
- Chemokine-expressing bacteria represent a promising, well-tolerated platform for cancer treatment.
