治療細胞增生異常之方法與組合物

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

096131735

專利證號

I 359030

專利獲證名稱

治療細胞增生異常之方法與組合物

專利所屬機關 (申請機關)

國立臺灣大學

獲證日期

2012/03/01

技術說明

本研究發展利用腺病毒載體分別攜帶GM-CSF、IL-12、ED或PEDF基因，針對帶有原位肝腫瘤的動物模式進行基因治療實驗。腺病毒載體經由腫瘤內注射或是由肝動脈內注射。實驗結果顯示合併 GM-CSF 及 IL-12等細胞激素與ED及PEDF等抗血管生成因子的效果對接種式的腫瘤，或是由致癌物所引起之原生多發性肝腫瘤均有明顯縮小或清除的效果。經過治療之動物其存活率及存活時間明顯增加或增長。除了在小鼠(接種式的腫瘤)或在大鼠(多發性肝腫瘤)中有明顯的效果，我們發現這種合併式細胞激素基因治療法對於土撥鼠由肝炎病毒所引起之自發性肝癌也有明顯縮小或清除的效果。總結，這種合併式的基因治療法有極大的潛能開發成為臨床上治療肝腫瘤的策略。 The invention discovered that an adenoviral vector-mediated cocktail-type gene therapy strategy, combining immunotherapy [e.g., GMC-SF and IL-12 cytokine gene therapy] and antiangiogenic gene therapy [e.g., ED and PEDF gene therapy], could significantly and synergistically regress orthotpic liver tumors in several animal models as compared to either type of gene therapy strategy. The tumor models included the implanted orthotopic liver model in mice, the chemical-induced primary, multifocal liver tumor model in rats, and the woodchuck hepatic B virus-induced, spontaneously occurring liver tumors in woodchucks. The tumor-bearing animals treated with the combination gene therapy strategy exhibited significantly higher survival rates and longer survival time compared to the control groups. The 4-in-1 gene therapy strategy is particularly useful for the treatment of HCCs with large tumor burdens, and would encourage future clinical application as a neoadjuvant therapy.

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