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首页> 外文期刊>Clinical & developmental immunology. >A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro
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A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro

机译:人/鼠嵌合Fab抗体中和炭疽致死毒素体外

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Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of 3.46 × 10~(7)?L/mol and could neutralize LeTx with an EC_(50)of 85? μ g/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro . The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.
机译:暴露于炭疽芽孢杆菌引起的人炭疽感染不能总是用抗生素治疗。这主要是由于体内残留的炭疽毒素的影响。致命因子(LF)是致命毒素(LeTx)的成分,而致命毒素是炭疽毒素的主要毒力。在先前的研究中,产生了具有阻断活性的鼠抗LF鼠IgG单克隆抗体(mAb)(编码为LF8)。在此报告中,通过使用抗体工程技术将鼠类可变区插入人恒定区,从而减少鼠类人用抗体的不相容性,从LF8开发了人/鼠嵌合Fab mAb(编码为LF8-Fab)。在大肠杆菌中表达的LF8-Fab可以以3.46×10〜(7)?L / mol的亲和力特异性鉴定LF,并能以85?EC的EC_(50)中和LeTx。微克/毫升即使在不同时间点进行LeTx攻击后,LF8-Fab仍能在体外显示出对J774A.1细胞的保护。结果表明,LF8-Fab可能会得到进一步表征,并有可能用于抗炭疽感染的临床应用。

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