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Antitumor activity of interleukin 12 against interleukin 2-transduced mouse glioma cells
1The Institute of DNA Medicine, and Department of Neurosurgery, Jikei University, Tokyo, Japan. oncol-tk@po.iijnet.or.jp
Abstract:
We subcutaneously inoculated parental and glioma cells genetically engineered to express interleukin-2 (SR/IL-2) into syngeneic mice. The tumor growth of the transfectants was slower than that of the parental cells. We then stereotactically inoculated transfectants into the brains of mice. The survival of the mice injected with parental cells was shorter than that of the mice inoculated with transfectants. SR/IL-2 cells were inoculated subcutaneously into the flank of mice, after which rmIL-12 was administered intraperitoneally (i.p.). The resultant transient tumor growth was followed by regression. rmIL-12 or saline were then injected i.p. into mice that had been inoculated in the brain with SR/IL-2 cells. There was no significant difference in survival time between the treated and control groups.
Insights
Genetically engineered glioma cells expressing interleukin-2 (IL-2) showed slower tumor growth and improved survival in mice. However, treatment with recombinant interleukin-12 (rmIL-12) did not significantly impact survival in brain tumor models.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Glioma is a primary brain tumor with poor prognosis.
- Interleukin-2 (IL-2) and Interleukin-12 (IL-12) are cytokines with immunomodulatory properties.
- Gene engineering of tumor cells to express cytokines is a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the therapeutic potential of glioma cells engineered to express IL-2 (SR/IL-2) in syngeneic mouse models.
- To investigate the efficacy of recombinant IL-12 (rmIL-12) in combination with SR/IL-2 cells for glioma treatment.
Main Methods:
- Subcutaneous and stereotactic inoculation of parental and SR/IL-2 glioma cells into syngeneic mice.
- Administration of rmIL-12 intraperitoneally (i.p.) in flank and brain tumor models.
- Monitoring of tumor growth and animal survival.
Main Results:
- SR/IL-2 cells exhibited slower tumor growth compared to parental cells when inoculated subcutaneously.
- Mice inoculated intracranially with SR/IL-2 cells showed longer survival than those with parental cells.
- Intraperitoneal administration of rmIL-12 resulted in transient tumor growth regression in flank models but did not significantly improve survival in brain tumor models.
Conclusions:
- Glioma cells engineered to express IL-2 demonstrate oncolytic potential and can enhance survival in preclinical models.
- Systemic administration of rmIL-12 did not provide a significant survival benefit for intracranial gliomas in this study.
- Further research is warranted to optimize cytokine-based immunotherapies for glioblastoma treatment.