治疗性抗体免疫原性的研究进展

Research progress on immunogenicity of therapeutic antibodies

治疗性抗体在临床上获得了理想效果,但抗体药物的免疫原性可能引发机体抗药物免疫反应,从而诱导抗药抗体(anti-drug antibody,ADA)的产生。ADA通过中和/非中和药物活性,影响药物的清除和生物利用度,改变药物药代动力学和药效学特性。在临床中,ADA可干扰或阻断药物的治疗效果,并可能导致不同程度的不良反应;在临床前研究中,ADA可干扰候选分子的有效性评价和筛选。本文就影响治疗性抗体免疫原性的因素、ADA的类型及形成机制、ADA的检测方法、降低免疫原性的方法及针对高免疫原性药物的临床前动物模型研发作一综述,以期为治疗性抗体的研发提供参考。

Therapeutic antibodies have achieved ideal results in clinical practice,while the immunogenicity of antibody drugs may trigger anti-drug immune response in the body,thus inducing the formation of anti-drug antibody(ADA).ADA affects the clearance and bioavailability of drugs through neutralizing/non-neutralizing drug activities,and changes the pharmacokinetic and pharmacodynamic characteristics of drugs,which can interfere or block the therapeutic effect of drugs and may lead to adverse reactions to varying degrees in clinical practice,and can interfere with the effectiveness evaluation and screening of candidate molecules in preclinical studies.Therefore,this paper reviewed the factors affecting immunogenicity,the types and formation mechanism of ADA,the detection methods of ADA,the strategies to mitigate immunogenicity and the development of preclinical animal models for highly immunogenic drugs,so as to provide a reference for the development of therapeutic antibodies.