Interferon α2b gene delivery using adenoviral vector causes inhibition of tumor growth in xenograft models from a variety of cancers
Interferon α2b gene delivery using adenoviral vector causes inhibition of tumor growth in xenograft models from a variety of cancers
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DOI：
10.1038/sj.cgt.7700364
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发表时间：
2001-10-01
影响因子：
6.4
通讯作者：
Sugarman, BJ
中科院分区：
文献类型：
--
作者：
Ahmed, CMI;Johnson, DE;Sugarman, BJ
由巨细胞病毒启动子IACB驱动的表达人干扰素α 2b的重组腺病毒显示在体外和体内产生和分泌生物活性蛋白。在布法罗大鼠中静脉内给予IACB导致生物活性人干扰素的循环水平为70，000国际单位/mL，持续长达15天。IACB给药后干扰素蛋白的分布与皮下注射干扰素蛋白不同。与蛋白质递送相比，IACB递送后在肝脏和脾脏中观察到更高水平的干扰素蛋白。IACB的抗肿瘤功效，如通过抑制肿瘤生长所测量的，在具有来自不同类型的人癌症的已建立的人肿瘤异种移植物的无胸腺裸鼠中进行测试。对IACB瘤内给药最敏感的皮下肿瘤为U87 MG（胶质母细胞瘤）和K562（慢性髓性白血病），其次是Hep 3B（肝细胞癌）和LN 229细胞（胶质母细胞瘤）。在携带U87 MG或Hep 3B异种移植物的动物中静脉内施用IACB也有效抑制肿瘤生长，尽管程度低于瘤内施用。IACB还在用H69（小细胞肺癌）细胞产生的米色/SCID小鼠的转移模型中进行了测试，并发现其延长了荷瘤动物的存活期。这表明干扰素基因递送可以有效抑制多种细胞中的肿瘤生长。
A recombinant adenovirus expressing human interferon alpha 2b driven by the cytomegalovirus promoter, IACB, was shown to produce and secrete biologically active protein in vitro and in vivo. Intravenous administration of IACB in Buffalo rats resulted in circulating levels of biologically active human interferon at 70,000 international units/mL for up to 15 days. Distribution of interferon protein after IACB administration was different from that seen with the subcutaneous delivery of interferon protein. Higher levels of interferon protein were observed in liver and spleen after IACB delivery compared to protein delivery. The antitumor efficacy of IACB, as measured by suppression of tumor growth, was tested in athymic nude mice bearing established human tumor xenografts from different types of human cancer. Subcutaneous tumors most responsive to the intratumoral administration of IACB ranked as U87MG (glioblastoma) and K562 (chronic myelogenous leukemia), followed by Hep 3B (hepatocellular carcinoma) and LN229 cells (glioblastoma). Intravenous administration of IACB in animals bearing U87MG or Hep 3B xenografts was also effective in Suppressing tumor growth, although to a lesser extent than the intratumoral administration. IACB was also tested in a metastatic model in beige/SCID mice generated with H69 (small cell lung carcinoma) cells and was found to prolong survival in tumor-bearing animals. This suggested that interferon gene delivery can be effective in suppressing tumor growth in a wide variety of cells.