Attenuated Salmonella typhimurium with interleukin 2 gene prevents the establishment of pulmonary metastases in a model of osteosarcoma

Brent S. Sorenson, Kaysie L Banton, Natalie L. Frykman, Arnold S. Leonard, Daniel A Saltzman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Purpose: The current management of osteosarcoma (OS) entails an aggressive preoperative and postoperative chemotherapeutic regimen with limb salvage surgery. Despite these efforts, relapse-free survival is less than 60% in patients with classic OS, whereas most patients relapse with pulmonary metastases. In these studies, we sought to prevent the establishment of pulmonary metastases from OS with a single oral dose of SalpIL2. Methods: Mice were administered attenuated Salmonella typhimurium with (SalpIL2) and without a gene for human interleukin 2 (Sal-NG) 7 days before challenge with 2 × 105 OS cells via tail vein. Three weeks after injection, mice were harvested for splenic lymphocytes and tumor enumeration. Results: Prophylaxis with attenuated SalpIL2 significantly reduces pulmonary metastases in number and volume (P < .0001 and P < .0001) with respect to saline controls. Furthermore, splenic natural killer cell populations were increased 396% with SalpIL2 (P < .0007) and 426% with Sal-NG (P < .0003) compared to nontreated groups. Conclusions: Host natural killer response is greatly amplified and maybe partially responsible for the effective immune response against the formation of pulmonary metastases. A single oral dose of SalpIL2 may be a novel form of adjuvant therapy for patients after early detection of primary OS.

Original languageEnglish (US)
Pages (from-to)1153-1158
Number of pages6
JournalJournal of Pediatric Surgery
Volume43
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Interleukin 2
  • Natural killer cells
  • Osteosarcoma
  • Salmonella typhimurium

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