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 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.
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 humaninterleukin 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.
Authors: Michael John Mertensotto; Jeremy J Drees; Lance B Augustin; Janet L Schottel; Daniel A Saltzman Journal: Curr Microbiol Date: 2014-11-29 Impact factor: 2.188
Authors: Brent S Sorenson; Kaysie L Banton; Lance B Augustin; Arnold S Leonard; Daniel A Saltzman Journal: Onco Targets Ther Date: 2011-05-30 Impact factor: 4.147
Authors: Sara E Fritz; Michael S Henson; Emily Greengard; Amber L Winter; Kathleen M Stuebner; Una Yoon; Vicki L Wilk; Antonella Borgatti; Lance B Augustin; Jaime F Modiano; Daniel A Saltzman Journal: Vet Med Sci Date: 2016-06-06
Authors: Neil S Forbes; Robert S Coffin; Liang Deng; Laura Evgin; Steve Fiering; Matthew Giacalone; Claudia Gravekamp; James L Gulley; Hal Gunn; Robert M Hoffman; Balveen Kaur; Ke Liu; Herbert Kim Lyerly; Ariel E Marciscano; Eddie Moradian; Sheryl Ruppel; Daniel A Saltzman; Peter J Tattersall; Steve Thorne; Richard G Vile; Halle Huihong Zhang; Shibin Zhou; Grant McFadden Journal: J Immunother Cancer Date: 2018-08-06 Impact factor: 13.751