Carrasco-Triguero Montserrat, Dere Randall C, Milojic-Blair Marija, Saad Ola M, Nazzal Denise, Hong Kyu, Kaur Surinder
Department of BioAnalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Bioanalysis Department, Immune-Onc Therapeutics, Inc., 4030 Fabian Way, Palo Alto, CA 94303, USA.
Bioanalysis. 2019 Sep;11(17):1555-1568. doi: 10.4155/bio-2018-0259. Epub 2019 Jun 18.
To evaluate the clinical immunogenicity of eight antibody-drug conjugates (ADCs), multi-domain biotherapeutics that could theoretically pose a greater immunogenicity risk than monoclonal antibodies (mAbs) because they contain non-natural structural motifs. Immunogenicity strategies and assays for these ADCs included those commonly used for conventional biotherapeutics with additional characterization. A tiered approach was adopted for testing Phase I and II clinical study samples with screening, confirmatory assays and additional domain characterization. Antidrug antibody incidences with these ADCs were within those reported for mAb biotherapeutics with no apparent impact on clinical outcomes. These data suggest that the ADC hapten-like structure across these eight ADCs does not appear to increase patient immune responses beyond those generally observed for mAb biotherapeutics.
为评估八种抗体药物偶联物（ADC）的临床免疫原性，多结构域生物治疗药物理论上可能比单克隆抗体（mAb）带来更大的免疫原性风险，因为它们包含非天然结构基序。这些ADC的免疫原性策略和检测方法包括常用于传统生物治疗药物的方法以及额外的特性鉴定。采用分层方法对I期和II期临床研究样本进行检测，包括筛选、确证检测和额外的结构域特性鉴定。这些ADC的抗药抗体发生率在mAb生物治疗药物报告的范围内，对临床结果没有明显影响。这些数据表明，这八种ADC的类半抗原结构似乎不会使患者的免疫反应比mAb生物治疗药物普遍观察到的反应增加。
