Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model

Brent Sorenson, Kaysie Banton, Lance Augustin, Sean Barnett, Karen McCulloch, Joshua Dorn, Natalie Frykman, Arnold Leonard, Daniel SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Salmonella enterica serovar Typhimurium preferentially colonizes tum...

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Autores principales:	Brent Sorenson, Kaysie Banton, Lance Augustin, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/36b87085e0e14ada89ca16fd5b9f0bfa
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spelling	oai:doaj.org-article:36b87085e0e14ada89ca16fd5b9f0bfa2021-12-02T00:10:30ZSafety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model1177-54751177-5491https://doaj.org/article/36b87085e0e14ada89ca16fd5b9f0bfa2010-03-01T00:00:00Zhttp://www.dovepress.com/safety-and-immunogenicity-of-salmonella-typhimurium-expressing-c-termi-a4099https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Brent Sorenson, Kaysie Banton, Lance Augustin, Sean Barnett, Karen McCulloch, Joshua Dorn, Natalie Frykman, Arnold Leonard, Daniel SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Salmonella enterica serovar Typhimurium preferentially colonizes tumors in vivo and has proven to be an effective biologic vector. The attenuated S. enterica Typhimurium strain &chi;4550 was engineered to express truncated human interleukin-2 and renamed SalpIL2. Previously, we observed that a single oral administration of SalpIL2 reduced tumor number and volume, while significantly increasing local and systemic natural killer (NK) cell populations in an experimental metastasis model. Here we report that in nontumor-bearing mice, a single oral dose of SalpIL2 resulted in increased splenic cytotoxic T and NK cell populations that returned to control levels by 4 weeks post oral administration. Though SalpIL2 was detected in mouse tissues for up to 10 weeks, no prolonged alterations in peripheral blood serum chemistry or complete blood cell counts were observed. Similarly, comparative histopathological analysis of tissues revealed no significant increase in pyogranulomas in SalpIL2-treated animals with respect to saline controls. In Rag-1 knockout mice, which have severely impaired B and T cell function, SalpIL2 reduced growth of hepatic metastases. Furthermore, SalpIL2 altered expression of several proinflammatory cytokines and chemokines in the serum of mice with pulmonary osteosarcoma metastases. These data further suggest that SalpIL2 is avirulent and induces a cell-mediated antitumor response.Keywords: Salmonella Typhimurium, natural killer cells, interleukin-2 Brent SorensonKaysie BantonLance Augustinet alDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2010, Iss default, Pp 61-73 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Brent Sorenson Kaysie Banton Lance Augustin et al Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
description	Brent Sorenson, Kaysie Banton, Lance Augustin, Sean Barnett, Karen McCulloch, Joshua Dorn, Natalie Frykman, Arnold Leonard, Daniel SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Salmonella enterica serovar Typhimurium preferentially colonizes tumors in vivo and has proven to be an effective biologic vector. The attenuated S. enterica Typhimurium strain &chi;4550 was engineered to express truncated human interleukin-2 and renamed SalpIL2. Previously, we observed that a single oral administration of SalpIL2 reduced tumor number and volume, while significantly increasing local and systemic natural killer (NK) cell populations in an experimental metastasis model. Here we report that in nontumor-bearing mice, a single oral dose of SalpIL2 resulted in increased splenic cytotoxic T and NK cell populations that returned to control levels by 4 weeks post oral administration. Though SalpIL2 was detected in mouse tissues for up to 10 weeks, no prolonged alterations in peripheral blood serum chemistry or complete blood cell counts were observed. Similarly, comparative histopathological analysis of tissues revealed no significant increase in pyogranulomas in SalpIL2-treated animals with respect to saline controls. In Rag-1 knockout mice, which have severely impaired B and T cell function, SalpIL2 reduced growth of hepatic metastases. Furthermore, SalpIL2 altered expression of several proinflammatory cytokines and chemokines in the serum of mice with pulmonary osteosarcoma metastases. These data further suggest that SalpIL2 is avirulent and induces a cell-mediated antitumor response.Keywords: Salmonella Typhimurium, natural killer cells, interleukin-2
format	article
author	Brent Sorenson Kaysie Banton Lance Augustin et al
author_facet	Brent Sorenson Kaysie Banton Lance Augustin et al
author_sort	Brent Sorenson
title	Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
title_short	Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
title_full	Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
title_fullStr	Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
title_full_unstemmed	Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model
title_sort	safety and immunogenicity of salmonella typhimurium expressing c-terminal truncated human il-2 in a murine model
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/36b87085e0e14ada89ca16fd5b9f0bfa
work_keys_str_mv	AT brentsorenson safetyandimmunogenicityofsalmonellatyphimuriumexpressingcterminaltruncatedhumanil2inamurinemodel AT kaysiebanton safetyandimmunogenicityofsalmonellatyphimuriumexpressingcterminaltruncatedhumanil2inamurinemodel AT lanceaugustin safetyandimmunogenicityofsalmonellatyphimuriumexpressingcterminaltruncatedhumanil2inamurinemodel AT etal safetyandimmunogenicityofsalmonellatyphimuriumexpressingcterminaltruncatedhumanil2inamurinemodel
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Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model

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