title: Safety and immunogenicity of Salmonella typhimurium expressing C-terminal truncated human IL-2 in a murine model.
abstract: Salmonella enterica serovar Typhimurium preferentially colonizes tumors in vivo and has proven to be an effective biologic vector. The attenuated S. enterica Typhimurium strain chi4550 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.
authors.affiliation: Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Sorenson
authors.forename: Kaysie
authors.initials: K
authors.lastname: Banton
authors.forename: Lance
authors.initials: L
authors.lastname: Augustin
authors.forename: Sean
authors.initials: S
authors.lastname: Barnett
authors.forename: Karen
authors.initials: K
authors.lastname: McCulloch
authors.forename: Joshua
authors.initials: J
authors.lastname: Dorn
authors.forename: Natalie
authors.initials: N
authors.lastname: Frykman
authors.forename: Arnold
authors.initials: A
authors.lastname: Leonard
authors.forename: Daniel
authors.initials: D
authors.lastname: Saltzman