Attenuated Salmonella typhimurium with interleukin 2 gene prevents the establishment of pulmonary metastases in a model of osteosarcoma.
OBJECTIVE
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 x 10(5) 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.
Department of Surgery, Division of Pediatric Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Brent S
BS
Sorenson
Kaysie L
KL
Banton
Natalie L
NL
Frykman
Arnold S
AS
Leonard
Daniel A
DA
Saltzman
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001859:Bone Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D012516:Osteosarcoma / Q000473:pathology / Q000556:secondary*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012486:Salmonella typhimurium / Q000235:genetics*; D012680:Sensitivity and Specificity; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D007376:Interleukin-2