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    • 3. 发明申请
    • INTERFERON ALPHA AND ANTISENSE K-RAS RNA COMBINATION GENE THERAPY
    • 干扰素和抗原K-RAS RNA组合基因治疗
    • US20090175825A1
    • 2009-07-09
    • US12390091
    • 2009-02-20
    • Kazunori AOKITeruhiko Yoshida
    • Kazunori AOKITeruhiko Yoshida
    • A61K38/21A61P35/00
    • C12N15/1135A61K48/005C12N2310/11C12N2310/111C12N2320/31
    • An antiproliferative effect of IFN-α gene transduction in pancreatic cancer cells. The invention relates to expression of IFN-α to effectively induce growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another aspect of the invention relates to targeting the characteristic genetic aberration, K-ras point mutation, in pancreatic cancer, and that the expression of antisense K-ras RNA significantly suppresses the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K-ras RNA significantly enhanced IFN-α-induced cell death (1.3-3.5 fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. The invention also relates to a method of suppressing pancreatic cancer cells using double strand RNA formed by antisense and endogeneous K-ras RNA in combination with the anti-tumor activity of IFN-α. The invention relates to the combination of IFN-α and antisense K-ras RNA as an effective gene therapy strategy against pancreatic cancer. The invention also relates to a method of treating pancreatic cancer cells disseminated throughout the body by administering the inventive combination to localized pancreatic cancer cell tumor. The invention also relates to inducing indirect immunological antitumor activity to provide systemic immunity against pancreatic cancer cells.
    • IFN-α基因转导在胰腺癌细胞中的抗增殖作用。 本发明涉及IFN-α的表达,以有效诱导胰腺癌细胞的生长抑制和细胞死亡,与其他类型的癌症和正常细胞相比,这种作用似乎更加突出。 本发明的另一方面涉及靶向胰腺癌中的特征性遗传差异K-ras点突变,反义K-ras RNA的表达显着抑制胰腺癌细胞的生长。 当这两种基因治疗策略相结合时,反义K-ras RNA的表达显着增强了IFN-α诱导的细胞死亡(1.3-3.5倍),并抑制了小鼠胰腺癌细胞的皮下生长。 本发明还涉及使用由反义和内源K-ras RNA形成的双链RNA与IFN-α的抗肿瘤活性组合来抑制胰腺癌细胞的方法。 本发明涉及IFN-α和反义K-ras RNA的组合,作为对胰腺癌的有效基因治疗策略。 本发明还涉及通过将本发明组合施用于局部胰腺癌细胞肿瘤来治疗遍及全身的胰腺癌细胞的方法。 本发明还涉及诱导间接免疫抗肿瘤活性以提供对胰腺癌细胞的全身免疫。