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The clearance kinetics of autologous RhD-positive erythrocytes coated ex vivo with novel recombinant and monoclonal anti-D antibodies

机译:新型重组和单克隆抗D抗体离体包裹的自体RhD阳性红细胞的清除动力学

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摘要

Anti-D is given routinely to pregnant RhD-negative women to prevent haemolytic disease of the fetus and newborn. To overcome the potential drawbacks associated with plasma-derived products, monoclonal and recombinant forms of anti-D have been developed. The ability of two such antibodies, BRAD-3/5 monoclonal anti-D IgG (MAD) and rBRAD-3/5 recombinant anti-D IgG (RAD), to clear RhD-positive erythrocytes from the circulation was compared using a dual radiolabelling technique. Six RhD-positive males received autologous erythrocytes radiolabelled with 99mTc and 51Cr and coated ex vivo with MAD and RAD. Blood samples were collected up to 1 h following intravenous injection, and percentage dose of radioactivity in the samples determined. Three different levels of coating were used on three separate occasions. No significant differences between MAD and RAD were observed in the initial clearance rate constant at any dose level. The log[activity]-time clearance plots were curved, showing a reduction in the clearance rate constant with time. This reduction was more marked for RAD than for MAD. The results support a dynamic model for the clearance of antibody-coated erythrocytes that may have wider relevance for the therapeutic use of antibodies.
机译:常规向孕妇RhD阴性的妇女服用抗D素,以预防胎儿和新生儿的溶血性疾病。为了克服与血浆来源的产品相关的潜在缺点,已经开发了抗D的单克隆和重组形式。使用双重放射性标记比较了两种抗体BRAD-3 / 5单克隆抗D IgG(MAD)和rBRAD-3 / 5重组抗D IgG(RAD)从循环中清除RhD阳性红细胞的能力。技术。六名RhD阳性男性接受了以 99m Tc和 51 Cr放射性标记的自体红细胞,并在体外用MAD和RAD进行了包被。在静脉内注射后直至1小时,收集血液样品,并确定样品中放射性百分比剂量。在三种不同的情况下使用了三种不同水平的涂料。在任何剂量水平下,初始清除率常数均未观察到MAD和RAD之间的显着差异。对数-时间清除率曲线是弯曲的,显示清除率常数随时间降低。 RAD的减少比MAD的减少更多。结果支持清除抗体涂层的红细胞的动态模型,该模型可能与抗体的治疗用途具有更广泛的相关性。

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