Toxicology and efficacy of tumor-targeting Salmonella typhimurium A1-R compared to VNP 20009 in a syngeneic mouse tumor model in immunocompetent mice
Salmonella typhimurium A1-R (S. typhimurium A1-R) attenuated by leu and arg auxotrophy has been shown to target multiple types of cancer in mouse models. In the present study, toxicologic and biodistribution studies of tumor-targeting S. typhimurium A1-R and S. typhimurium VNP20009 (VNP 20009) were performed in a syngeneic tumor model growing in immunocompetent BALB/c mice. Single or multiple doses of S. typhimurium A1-R of 2.5 × 105 and 5 × 105 were tolerated. A single dose of 1 × 106 resulted in mouse death. S. typhimurium A1-R (5 × 105 CFU) was eliminated from the circulation, liver and spleen approximately 3-5 days after bacterial administration via the tail vein, but remained in the tumor in high amounts. S. typhimurium A1-R was cleared from other organs much more rapidly. S. typhimurium A1-R and VNP 20009 toxicity to the spleen and liver was minimal. S. typhimurium A1-R showed higher selective targeting to the necrotic areas of the tumors than VNP20009. S. typhimurium A1-R inhibited the growth of CT26 colon carcinoma to a greater extent at the same dose of VNP20009. In conclusion, we have determined a safe dose and schedule of S. typhimurium A1-R administration in BALB/c mice, which is also efficacious against tumor growth. The results of the present report indicate similar toxicity of S. typhimurium A1-R and VNP20009, but greater antitumor efficacy of S. typhimurium A1-R in an immunocompetent animal. Since VNP2009 has already proven safe in a Phase I clinical trial, the present results indicate the high clinical potential of S. typhimurium A1-R.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Oncotarget - 8(2017), 33 vom: 15. Aug., Seite 54616-54628 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yong [VerfasserIn] |
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| Links: |
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| Themen: |
Biodistribution |
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| Anmerkungen: |
Date Completed 25.09.2017 Date Revised 13.11.2018 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.18632/oncotarget.17605 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM275741745 |
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| 245 | 1 | 0 | |a Toxicology and efficacy of tumor-targeting Salmonella typhimurium A1-R compared to VNP 20009 in a syngeneic mouse tumor model in immunocompetent mice |
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| 520 | |a Salmonella typhimurium A1-R (S. typhimurium A1-R) attenuated by leu and arg auxotrophy has been shown to target multiple types of cancer in mouse models. In the present study, toxicologic and biodistribution studies of tumor-targeting S. typhimurium A1-R and S. typhimurium VNP20009 (VNP 20009) were performed in a syngeneic tumor model growing in immunocompetent BALB/c mice. Single or multiple doses of S. typhimurium A1-R of 2.5 × 105 and 5 × 105 were tolerated. A single dose of 1 × 106 resulted in mouse death. S. typhimurium A1-R (5 × 105 CFU) was eliminated from the circulation, liver and spleen approximately 3-5 days after bacterial administration via the tail vein, but remained in the tumor in high amounts. S. typhimurium A1-R was cleared from other organs much more rapidly. S. typhimurium A1-R and VNP 20009 toxicity to the spleen and liver was minimal. S. typhimurium A1-R showed higher selective targeting to the necrotic areas of the tumors than VNP20009. S. typhimurium A1-R inhibited the growth of CT26 colon carcinoma to a greater extent at the same dose of VNP20009. In conclusion, we have determined a safe dose and schedule of S. typhimurium A1-R administration in BALB/c mice, which is also efficacious against tumor growth. The results of the present report indicate similar toxicity of S. typhimurium A1-R and VNP20009, but greater antitumor efficacy of S. typhimurium A1-R in an immunocompetent animal. Since VNP2009 has already proven safe in a Phase I clinical trial, the present results indicate the high clinical potential of S. typhimurium A1-R | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a VNP20009 | |
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| 700 | 1 | |a Cao, Wenluo |e verfasserin |4 aut | |
| 700 | 1 | |a Toneri, Makoto |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Kiyuna, Tasuku |e verfasserin |4 aut | |
| 700 | 1 | |a Murakami, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Nelson, Scott D |e verfasserin |4 aut | |
| 700 | 1 | |a Dry, Sarah M |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yunfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shukuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoen |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Huaiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Arun S |e verfasserin |4 aut | |
| 700 | 1 | |a Eilber, Fritz C |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffman, Robert M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ming |e verfasserin |4 aut | |
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