生物技术药物免疫原性的评价及面临的挑战

Current status and challenge of biopharmaceutical immunogenicity

随着大量生物技术药物的研发,免疫原性的评价成为阐明这些药物临床安全性和有效性的关键因素。评价非期望出现的免疫原性是生物技术药物临床前和临床评价的重要内容。完整的免疫原性评价应是方法学的验证,选择合理的免疫学和生物学方法检测抗体滴度的变化及分析抗体亚型和特性、测定抗体的中和活性、免疫复合物的形成及沉积,分析抗体产生对药物药动学、药效和毒性反应等影响。目前免疫原性评价面临的挑战是免疫学检测方法的优化以及提高动物和体外模型的预测性。

The primary concerns of unwanted immunogenicity for the efficacy and safety of biopharmaceuticals have been increasing over the past decade as the upsurge of biotechnology-derived therapeutics increases in clinical and non-clinical environments. The immunogenicity assessments include validation of methodology, selection of appropriate immunoassays and bioassays to measure and characterize antibodies and their subtypes against biopharmaceuticals, determination of antibody neutralization and formation and deposits of immune complexes as well as the analyses of relationship of antibody formation to pharmacokinetics and pharmacodynamic parameter and toxicities of drugs. Both optimization of available laboratory assay methods and predictability of immunogenicity with available animal models in vitro are currently the two major challenges in the assessment of immunogenicity for biological and clinical properties of biopharmaceuticals.