Introduction of cytokine genes into rat solid neoplasms with a hand-held gene gun:I. Effect of IL-12 plus TNF-α gene transfection on subcutaneous tumor

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Using a hand-held gene gun which accelerates DNA-coated microparticles, we examined the effect of interleukin-12 (IL-12) and/or tumor necrosis factor-α (TNF-α) gene transfection a rat solid tumor model. Yoshida sarcoma cells were inoculated subcutaneously into the chests of Donryu rats. Then 4μg of IL-12 and/or TNF-α DNA-coated gold (Au) particles was injected into the tumor by pressurized helium (He) gas at 400psi (1psi=6, 890Pa) on day 5 and 7 after tumor inoculation. The corresponding dose of β-galactosidase was given as a control. Compared with the control, injection of TNF-α, IL-12, and IL-12 plus TNF-α effectively inhibited tumor growth and improved the survival rate. TNF-α alone prolonged the survival of tumor-bearing rats, but the animals still died within 41 days after tumor injection, On the other hand, IL-12 alone and IL-12 plus TNF-α completely cured 20% and 40% of the rats, respectively. IL-12 plus TNF-α gene therapy using the gene gun showed a synergetic effect on the survival of tumor-bearing rats. This procedure might useful for the clinical treatment of solid cancer. In particular, there is a possibility of intraoperative gene transfection because the gene gun can introduce multiple genes very rapidly.
日本癌病態治療研究会の論文