E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors
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DOI:
10.1089/10430340150218369
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发表时间:
2001-02-10
期刊:
影响因子:
4.2
通讯作者:
Jensen, SL
Jensen, SL
中科院分区:
医学2区
文献类型:
--
作者:
Habib, NA;Sarraf, CE;Jensen, SL

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临床研究使用E1B 55-kDa缺失的重组突变腺病毒dl1520进行,以评估其对不可切除的原发性和继发性肝肿瘤患者的毒性和疗效。一项I期研究表明,dl1520在直接瘤内、动脉内或静脉注射时耐受性良好,剂量为3 × 10(11) PFU。组织超微结构检查显示,在细胞核周围的细胞质中存在腺病毒,并显示病毒感染后细胞死亡的两个不同终点:a期TI研究表明,当将dl1520和5-氟尿嘧啶(5-FU)联合输注到肝动脉中时,耐受性良好。为了获得更好的临床反应,需要进一步改进重组载体的设计。
Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU, Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis, A phase TI study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.