More than 25 therapeutic monoclonal antibodies (mAbs) used in oncology have been approved since 1997. Their nature has been largely modified through the last 20 years, from the chimeric IgG1 rituximab with pharmacokinetic parameters specific of murin or chimeric mAbs to humanized or human mAbs. Doses and administration frequency have been chosen based on this nature. More recently, the developed and registered mAbs are mostly IgG1, IgG2, IgG3 or IgG4 humanized or 100% human. Therefore, their behavior is different from the first mAbs authorized leading to lower systemic clearance and shorter half-life due to higher cellular uptake balanced by FcRn recognition with recirculation. The complexity of the pharmacokinetics and the pharmacokinetics/pharmacodynamics relation are increased for antibody-drug conjugates or bispecific T-cell engagers. However, significant number of studies reported pharmacokinetics/pharmacodynamics relations, with positive exposure-response link justifying the exploration of the pharmacokinetics in routine clinical practice of these therapeutic mAbs to prevent treatment failures and to limit their toxicities.

中文翻译：

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肿瘤学中使用的治疗性单克隆抗体的药代动力学/药效关系：第1部分，单克隆抗体，抗体-药物结合物和双特异性T细胞接合剂。

自1997年以来，已经批准了超过25种用于肿瘤的治疗性单克隆抗体（mAb）。在过去的20年中，其性质已经得到了很大的改变，从具有murin或嵌合mAb特有的药代动力学参数的嵌合IgG1利妥昔单抗到人源化或人类mAb。基于这种性质选择剂量和给药频率。最近，已开发和注册的mAb主要是人源化或100％人源的IgG1，IgG2，IgG3或IgG4。因此，它们的行为与获批的首批mAb不同，这是由于循环摄取FcRn所平衡的较高细胞摄取导致较低的系统清除率和较短的半衰期。对于抗体-药物缀合物或双特异性T细胞接合剂，药代动力学的复杂性和药代动力学/药效学关系增加。然而，