Preclinical pharmacology and toxicology evaluation of an anti-CD52 monoclonal antibody produced by perfusion fermentation process.
Preclinical pharmacology and toxicology evaluation of an anti-CD52 monoclonal antibody produced by perfusion fermentation process.
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DOI：
10.1093/jimb/kuab078
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发表时间：
2021-12-23
影响因子：
3.4
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Wang Y;Zheng C;Zhuang C;Fu Q;Qin J;Zhang B;Bian Y;Qi N;Zhu J
抗CD52单抗用于慢性淋巴细胞白血病和多发性硬化症的治疗。在此之前，我们开发了一种灌流工艺来生产名为“Mab-TH”的类似生物的单抗。在结构鉴定、纯度分析和活性测量领域进行了一系列质量评估。在这些质量研究之后，本报告侧重于临床前药理学和毒理学评价。与原药alemtuzumab相比，MAB-TH具有生物学、药理学和毒理学特性。结合活性和免疫依赖毒性作为体外活性进行评价。移植人白血病细胞系的严重免疫缺陷小鼠也被用作体内药理模型，并在食蟹猴体内进行了为期4周的重复给药研究，以评估安全性差异。我们的结果表明，通过灌流过程产生的抗CD52抗体Mab-TH在体内外活性方面与相关临床前模型中的Alemtuzumab具有很高的相似性。结果支持将其作为临床评价的生物相似候选者。
Anti-cluster of differentiation 52 (CD52) monoclonal antibody (mAb) has been employed in the treatment of chronic lymphoblastic leukemia and multiple sclerosis. Previously we developed a perfusion process to produce the biosimilar mAb named “Mab-TH.” A series of quality assessments was conducted in the fields of structural identification, purity analysis, and activity measurement. After these quality researches, this report laid emphasis on preclinical pharmacology and toxicology evaluation. Mab-TH was characterized in biological, pharmacological, and toxicological properties in comparison with the original drug, alemtuzumab. Binding activity and immune-dependent toxicity as in vitro activity were evaluated. Severe immunodeficient mice transplanted with a human leukemia cell line were also used as an in vivo pharmacological model and a 4-week repeated dosing study in cynomolgus monkeys was conducted to evaluate the safety differences. Our results demonstrated that Mab-TH, the anti-CD52 antibody generated by a perfusion process, had high similarity in in vitro and in vivo activities compared with alemtuzumab in relevant preclinical models. The results supported it as a biosimilar candidate for clinical evaluation.
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