抗体药物免疫原性评估的研究进展

Research Progress on Immunogenicity Evaluation of Antibodies

抗体药物引发机体产生的非必要免疫反应,将影响药物的疗效和安全性。因此,有必要对处于不同研发阶段的抗体药物的免疫原性进行评估,包括上市后的监测。免疫原性评价是所有抗体药物研发过程中的关键环节,监管部门对抗体药物的免疫原性评估有严格要求,但是对于证据类型,数量和质量缺少统一标准,也缺少抗体药物免疫原性测定实验设计的指导文件或免疫原性比较的标准。新技术的出现促进了免疫原性评估的发展,免疫原性检出率也有了相应的提高,因此,只能进行“头对头”临床试验,才能对抗体药物的免疫原性进行评估。因此,研究机构,监管机构和临床医生都需要认识到免疫原性分析方法的变化。在这里,讨论了抗体药物免疫原性的相关因素,潜在的临床后果,评估免疫原性的监管指导变化,非临床和临床研究的免疫原性评估方法的发展,以及生物仿制药免疫原性评估需要特别注意的事项。

Antibodies trigger unwanted immune response, which influence the efficacy and safety of drugs. Therefore, it is necessary to evaluate immunogenicity of antibodies in different stage of development, including post-marketing surveillance. Immunogenicity evaluation is the key step in the development of all antibodies. The regulatory- authorities have strict requirements on the immunogenicity of antibodies products for evaluation, there is a lack of uniform standards for the type, quantity, and quality of evidence, but also the lack of immunogenicity of antibodies guidance documents or immunogenic experimental design standards. New technologies promote the development of immunogenicity evaluation, the detection rate of immunogenicity also rise, therefore ＂head to head＂ clinical trials to evaluate the immunogenicity of antibodies. Therefore, the regulators and clinicians need to be aware of the change of immunogenicity analysis. Here, the related factors of immunogenicity of antibodies, potential clinical consequences, changes of the current regulatory guidance and development of non clinical and clinical studies of imrnunogenicity evaluation methods were discussed. And a special note of immunogenicity evaluation on biosimilars was also discussed.