Attenuated Salmonella typhimurium with IL-2 gene reduces pulmonary metastases in murine osteosarcoma
Brent S Sorenson1, Kaysie L Banton, Natalie L Frykman
1Department of Surgery, University of Minnesota Medical School, 420 Delaware Street SE, MMC 195, Minneapolis, MN 55455, USA.
Abstract:
Historically, osteosarcoma has been a problematic metastatic disease, with 40-80% of patients developing pulmonary metastasis after primary tumor resection. Recent treatment advancements have reduced the occurrence of metastatic lesions to less than 30%. Using attenuated Salmonella typhimurium, we previously demonstrated regression in tumor burden in murine solid tumor and metastatic models. We established a murine model for metastatic osteosarcoma to determine the effect of treatment with a single oral dose of attenuated S. typhimurium with (SalpIL2) and without (Sal-NG) a gene for a truncated human interleukin-2. Female balb/c mice were administered 2 x 10(5) (ATCC K7M2) osteosarcoma cells via tail vein injection from culture and treated by oral gavage of Salmonella species 3 days later. Mice were harvested for splenic lymphocytes and tumor enumeration by intratracheal injection with India ink 21 days after injection. Treatment with attenuated SalpIL2 reduced pulmonary metastases in number and volume compared to saline controls. Furthermore, splenic natural killer cell populations were increased 93% with SalpIL2 and 114% with Sal-NG compared to nontreated groups. This pulmonary metastasis model demonstrates attenuated Salmonella typhimurium with human interleukin-2 reduced metastatic osteosarcoma in mice and confirm the need for further investigation into the immunologic properties of SalpIL2 as a possible treatment for metastatic osteosarcoma.
Insights
Attenuated Salmonella typhimurium, particularly with human interleukin-2 (SalpIL2), effectively reduced pulmonary metastases in a murine osteosarcoma model. This approach also enhanced natural killer cell activity, suggesting SalpIL2
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Osteosarcoma historically presents a high risk of pulmonary metastasis (40-80%).
- Recent advancements have decreased metastatic lesion occurrence to under 30%.
- Attenuated Salmonella typhimurium has shown promise in reducing tumor burden in preclinical models.
Purpose of the Study:
- To evaluate the efficacy of attenuated Salmonella typhimurium, with and without human interleukin-2 (SalpIL2 and Sal-NG), in a murine model of metastatic osteosarcoma.
- To assess the impact of SalpIL2 on pulmonary metastasis number and volume.
- To investigate the effect of SalpIL2 and Sal-NG on splenic natural killer cell populations.
Main Methods:
- Established a murine model by tail vein injection of osteosarcoma cells into female balb/c mice.
- Administered a single oral dose of attenuated Salmonella typhimurium (SalpIL2 or Sal-NG) or saline control.
- Quantified pulmonary metastases and analyzed splenic lymphocytes 21 days post-treatment.
Main Results:
- SalpIL2 treatment significantly reduced the number and volume of pulmonary metastases compared to saline controls.
- Splenic natural killer cell populations increased by 93% with SalpIL2 and 114% with Sal-NG.
- The study confirmed the therapeutic potential of attenuated Salmonella in reducing metastatic osteosarcoma burden.
Conclusions:
- Attenuated Salmonella typhimurium, especially SalpIL2, demonstrates significant potential in reducing metastatic osteosarcoma in mice.
- The observed increase in natural killer cells highlights the immunomodulatory effects of Salmonella treatment.
- Further research into SalpIL2's immunologic properties is warranted for its potential as a metastatic osteosarcoma therapy.
