Secretory production of biologically active rat interleukin-2 by Clostridium acetobutylicum DSM792 as tool for anti-tumor treatment

Secretory production of biologically active rat interleukin-2 by Clostridium acetobutylicum DSM792 as tool for anti-tumor treatment
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DOI:
10.1016/j.femsle.2005.03.037
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发表时间:
2005-05-01
影响因子:
2.1
通讯作者:
Anné, J
Anné, J
中科院分区:
生物学4区
文献类型:
--
作者:
Barbé, S;Van Mellaert, L;Anné, J

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在过去的十年中,对选择性地将高治疗剂量的抗癌剂递送至肿瘤的有效手段的研究已经探索了各种系统。静脉注射梭菌孢子的能力,渗透,从而选择性地在实体瘤的缺氧区域发芽是非常具体的,使这个系统的一个有趣的除了抗癌治疗武器库。为了增加可能用于癌症治疗的治疗性蛋白质的数量,我们已经测试了丙酮丁醇梭菌分泌大鼠白细胞介素-2(rIL 2)的可能性。因此,将rIL 2 cDNA置于糖丁醇梭菌的内切-β-1,4-葡聚糖酶启动子和信号序列的控制下。含有相关构建体的重组丙酮丁醇梭菌分泌高达800 μ g/l的生物活性rIL 2。获得的产量应足以引起体内效应。(c)2005年欧洲微生物学会。Elsevier B. V.出版,保留所有权利。
The search for effective means of selectively delivering high therapeutic doses of anti-cancer agents to tumors has explored a variety of systems in the last decade. The ability of intravenously injected clostridial spores to infiltrate and thence selectively germinate in the hypoxic regions of solid tumors is exquisitely specific, making this system an interesting addition to the anti-cancer therapy arsenal. To increase the number of therapeutic proteins potentially useful for cancer treatment we have tested the possibility of Clostridium acetobutylicum to secrete rat interleukin-2 (rIL2). Therefore, rIL2 cDNA was placed under the control of the endo-beta-1,4-glucanase promoter and signal sequence of C saccharobutylicum. Recombinant C acetobutylicum containing the relevant construct secreted up to 800 mu g l(-1) biologically active rIL2. The obtained yield should be sufficient to provoke in vivo effects. (c) 2005 European Microbiological Societies. Published by Elsevier B.V. All rights reserved.