Virulence-attenuatedSalmonellaengineered to secrete immunomodulators reduce tumour growth and increase survival in an autochthonous mouse model of breast cancer / Lance B. Augustin, Liming Milbauer, Sara E. Hastings, Arnold S. Leonard, Daniel A. Saltzman, Janet L. Schottel
Abstract The ultimate goal of bacterial based cancer therapy is to achieve non-toxic penetration and colonisation of the tumour microenvironment. To overcome this efficacy-limiting toxicity of anticancer immunotherapy, we have tested a therapy comprised of systemic delivery of a vascular disrupting agent to induce intratumoral necrotic space, cannabidiol to temporarily inhibit angiogenesis and acute inflammation, and a strain of Salmonella Typhimurium that was engineered for non-toxic colonisation and expression of immunomodulators within the tumour microenvironment. This combination treatment strategy was administered to transgenic mice burdened with autochthonous mammary gland tumours and demonstrated a statistically significant 64% slower tumour growth and a 25% increase in mean survival time compared to control animals without treatment. These experiments were accomplished with minimal toxicity as measured by less than 7% weight loss and a return to normal weight gain within three days following intravenous administration of the bacteria. Thus, non-toxic, robust colonisation of the microenvironment was achieved to produce a significant antitumor effect.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Journal of drug targeting - 29(2021), 4, Seite 430-438 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Augustin, Lance B. [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
Anti-CTLA-4 |
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| Umfang: |
1 Online-Ressource (9 p) |
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| doi: |
10.1080/1061186X.2020.1850739 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Virulence-attenuatedSalmonellaengineered to secrete immunomodulators reduce tumour growth and increase survival in an autochthonous mouse model of breast cancer |c Lance B. Augustin, Liming Milbauer, Sara E. Hastings, Arnold S. Leonard, Daniel A. Saltzman, Janet L. Schottel |
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| 520 | |a Abstract The ultimate goal of bacterial based cancer therapy is to achieve non-toxic penetration and colonisation of the tumour microenvironment. To overcome this efficacy-limiting toxicity of anticancer immunotherapy, we have tested a therapy comprised of systemic delivery of a vascular disrupting agent to induce intratumoral necrotic space, cannabidiol to temporarily inhibit angiogenesis and acute inflammation, and a strain of Salmonella Typhimurium that was engineered for non-toxic colonisation and expression of immunomodulators within the tumour microenvironment. This combination treatment strategy was administered to transgenic mice burdened with autochthonous mammary gland tumours and demonstrated a statistically significant 64% slower tumour growth and a 25% increase in mean survival time compared to control animals without treatment. These experiments were accomplished with minimal toxicity as measured by less than 7% weight loss and a return to normal weight gain within three days following intravenous administration of the bacteria. Thus, non-toxic, robust colonisation of the microenvironment was achieved to produce a significant antitumor effect | ||
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| 700 | 1 | |a Hastings, Sara E. |e verfasserin |4 aut | |
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| 700 | 1 | |a Saltzman, Daniel A. |e verfasserin |4 aut | |
| 700 | 1 | |a Schottel, Janet L. |e verfasserin |4 aut | |
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