Salinas-Jazmín Nohemi, González-González Edith, Vásquez-Bochm Luz X, Pérez-Tapia Sonia M, Velasco-Velázquez Marco A
Unit for Development and Research in Bioprocesses Unit (UDIBI), National School of Biological Sciences, National Polytechnic Institute (IPN), University of Mexico (UNAM); School of Chemistry, National Autonomous University of Mexico (UNAM).
Unit for Development and Research in Bioprocesses Unit (UDIBI), National School of Biological Sciences, National Polytechnic Institute (IPN), University of Mexico (UNAM).
J Vis Exp. 2017 May 4(123):55542. doi: 10.3791/55542.
Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab. The protocols allow the side-to-side comparison of a reference rituximab and a marketed rituximab biosimilar. The evaluated products showed differences both in target binding and CDC induction, suggesting that there are underlying physicochemical differences and highlighting the need to analyze the impact of those differences in the clinical setting. The methods reported here constitute simple and inexpensive in vitro models for the evaluation of the activity of rituximab biosimilars. Thus, they can be useful during biosimilar development, as well as for quality control in biosimilar production. Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.
治疗性单克隆抗体（mAb）与包括癌症在内的不同病症的治疗相关。制药公司开发生物类似单克隆抗体既是一个市场机遇，也是一种提高药物可及性和降低治疗相关成本的策略。此处详述的方案描述了利妥昔单抗在Daudi细胞中对靶标结合和补体依赖的细胞毒性（CDC）诱导作用的评估。这两种功能需要抗体的不同结构区域，并且与利妥昔单抗诱导的临床效果相关。这些方案允许对参考利妥昔单抗和市售的利妥昔单抗生物类似药进行并排比较。所评估的产品在靶标结合和CDC诱导方面均显示出差异，这表明存在潜在的物理化学差异，并突出了在临床环境中分析这些差异影响的必要性。此处报道的方法构成了用于评估利妥昔单抗生物类似药活性的简单且低成本的体外模型。因此，它们在生物类似药开发过程中以及生物类似药生产的质量控制方面可能会很有用。此外，所提出的方法可以推广到其他治疗性单克隆抗体。
