Antibody formation to human(ized) therapeutic antibodies in humans is highly skewed toward anti-idiotype responses, probably because the idiotype is the only 'foreign' part of the antibody molecule. Here, we analyzed antibody responses to F(ab')2 fragments of a panel of 17 human(ized) therapeutic antibodies in rabbits. Homology between the rabbit germline and the human(ized) antibodies is moderate not only for the variable domains (both the complementarity-determining regions and the framework regions), but also for the constant domains (66% or less). Nevertheless, we observed a highly skewed anti-idiotype response in all cases, with up to >90% of the antibodies directed toward the idiotype. These results indicate that the idiotype may be inherently immunodominant. We used these biased responses to raise monoclonal rabbit anti-idiotype antibodies against secukinumab, ustekinumab, reslizumab, mepolizumab, palivizumab, and dupilumab and demonstrate the potential to develop sensitive pharmacokinetic assays with these antibodies.

中文翻译：

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兔子的偏向性抗独特型反应导致对生物制剂的高亲和力单克隆抗体。

人类（化）治疗性抗体的抗体形成高度倾向于抗独特型反应，这可能是因为独特型是抗体分子的唯一“外来”部分。在这里，我们分析了兔子对一组 17 种人（化）治疗性抗体的 F(ab')2 片段的抗体反应。兔种系和人（化）抗体之间的同源性不仅对于可变域（互补决定区和框架区）而且对于恒定域（66% 或更少）都是中等的。尽管如此，我们在所有情况下都观察到高度倾斜的抗独特型反应，高达 > 90% 的抗体针对独特型。这些结果表明独特型可能具有固有的免疫优势。