曲妥珠单抗电荷变异体：理化性质和药代动力学研究。
Trastuzumab Charge Variants: a Study on Physicochemical and Pharmacokinetic Properties.
机构信息
Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran.
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
出版信息
Iran Biomed J. 2023 Mar 1;27(2 & 3):108-16. doi: 10.61186/ibj.3837.
BACKGROUND
Post-translational modifications in bioprocessing and storage of recombinant mAbs are the main sources of charge variants. While the profile of these kinds of variants is considered an important attribute for the therapeutic mAbs, there is controversy about their direct role in safety and efficacy. In this study, the physicochemical and pharmacokinetic (PK) properties of the separated charge variants belonging to a trastuzumab potential biosimilar, were examined.
METHODS
The acidic peaks, basic peaks, and main variants of trastuzumab were separated and enriched by semi-preparative weak cation exchange. A panel of analytical techniques was utilized to characterize the physicochemical properties of these variants. The binding affinity to HER2 and FcγRs and the PK parameters were evaluated for each variant.
RESULTS
Based on the results, the charge variants of the proposed biosimilar had no significant influence on the examined efficacy and PK parameters.
CONCLUSION
During the development and production of biosimilar monoclonal antibodies, evaluating the effect of their charge variants on efficacy and PK parameters is needed.
背景
在重组单克隆抗体的生物加工和储存过程中的翻译后修饰是电荷变异体的主要来源。虽然这些变异体的种类被认为是治疗性单克隆抗体的一个重要属性，但它们在安全性和疗效方面的直接作用仍存在争议。在这项研究中，研究了属于曲妥珠单抗潜在生物类似药的分离电荷变异体的物理化学和药代动力学（PK）特性。
方法
通过半制备弱阳离子交换分离和富集曲妥珠单抗的酸性峰、碱性峰和主要变异体。利用一系列分析技术来表征这些变异体的物理化学特性。评估了每种变异体与 HER2 和 FcγRs 的结合亲和力以及 PK 参数。
结果
根据结果，所提出的生物类似药的电荷变异体对所检查的疗效和 PK 参数没有显著影响。
结论
在生物类似药单克隆抗体的开发和生产过程中，需要评估其电荷变异体对疗效和 PK 参数的影响。
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