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Title:
Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth | Cancer Immunology, Immunotherapy
Description:
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-γ (INFγ), 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.
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article, google, scholar, pubmed, cas, typhimurium, cancer, salmonella, attenuated, chemokine, cells, ccl, tumor, immunol, loeffler, reed, tumors, antitumor, access, growth, bacteria, privacy, cookies, content, administration, cell, vivo, clin, med, information, publish, research, search, engineered, produce, july, lenegrate, krajewska, john, murine, chemokines, cxcl, open, res, sci, dendritic, lymphoid, strieter, analysis, data,
Topics {✒️}
multi-drug-resistant murine carcinomas tumor-targeting salmonella typhimurium month download article/chapter cell-dependent antitumor responses lymphocyte-specific cc chemokine ckbeta-11/mip-3beta/elc endothelial-target rickettsial infections increase anti-tumor activity article cancer immunology slc/6ckine/exodus2/tca4 vivo-derived dendritic cells vivo immuno-depletion experiments attenuated salmonella typhimurium genetically modified strain related subjects cxcl9/10-cxcr3 chemokine system attenuated salmonella engineered full article pdf salmonella typhimurium engineered anti-tumor activity privacy choices/manage cookies human il-1 beta interferon-inducible protein 10 superficial bladder cancer confers tumor immunity macrophage tumoricidal activities targeting tumor live animals antitumor agent vnp20009 preclinical models tumour progression recombinant therapeutic proteins article loeffler tumor growth attenuated strain attenuated bacteria salmonella typhimurium european economic area check access bacillus prodigosus t1g3 bladder tumours immunological urinary measurements highly efficient chemoattractant considered senior authors instant access chemokine ccl21 conditions privacy policy significant adverse effects dendritic cells author information authors
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headline:Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth
description: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-γ (INFγ), 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.
datePublished:2008-07-17T00:00:00Z
dateModified:2008-07-17T00:00:00Z
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Salmonella
CCL21
Cancer therapy
Bacterial therapy
Tumor targeting
Oncology
Immunology
Cancer Research
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headline:Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth
description: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-γ (INFγ), 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.
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dateModified:2008-07-17T00:00:00Z
pageStart:769
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Salmonella
CCL21
Cancer therapy
Bacterial therapy
Tumor targeting
Oncology
Immunology
Cancer Research
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