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治疗性抗体人源度评价与人源化的计算方法研究进展

Research Advancements in Computational Approaches for Evaluation of Degree of Humanness and Humanization of Therapeutic Antibodies

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【作者】 李文振周雨薇刘文雯黄健

【Author】 LI Wenzhen;ZHOU Yuwei;LIU Wenwen;HUANG Jian;School of Life Science and Technology, University of Electronic Science and Technology of China;

【通讯作者】 黄健;

【机构】 电子科技大学生命科学与技术学院

【摘要】 治疗性抗体已成为全球生物制药行业不可或缺的组成部分。如何从海量非人源抗体中选择出或者基于非人源的先导抗体设计出人源化程度高的抗体从而降低其免疫原性,这一问题已成为当今抗体药物开发领域的研究热点之一,相应的经验、实验及计算方法统称为抗体人源化技术。已有研究证明,在保持抗体特异性、亲和力和稳定性等特征的前提下,提高抗体人源度能够有效降低其免疫原性。抗体人源化相关计算方法主要涉及人源化抗体的设计、抗体人源度的计算与评价等。当前,许多计算工具已被证实为抗体人源化和人源度评价的有效工具。该文系统性概述了抗体人源化的理论依据以及基于此开发出的计算方法的发展历程,并讨论了相关计算方法研究的最新进展。

【Abstract】 Therapeutic antibodies have become the integral component of the global biopharmaceutical industry. The selection or design of highly humanized antibodies from a vast pool of non-human antibodies to reduce their immunogenicity has emerged as the prominent research focus in the field of antibody drug development. This area of study, encompassing experience, experiments, and calculation methods, is collectively referred to as antibody humanization technology. It has been demonstrated that enhancing the human-like characteristics of an antibody can effectively diminish its immunogenicity while preserving its specificity, affinity,and stability. The computational approach for antibody humanization primarily involves designing humanized antibodies and calculating and evaluating their degree of humanness. Currently, numerous computational tools have been proved the effective for both antibody humanization and evaluation purposes. This review comprehensively summarizes the theoretical foundation underlying antibody humanization along with the development of associated computational methodologies while discussing recent advancements in this domain.

【基金】 国家自然科学基金(62071099,62371112)
  • 【文献出处】 电子科技大学学报 ,Journal of University of Electronic Science and Technology of China , 编辑部邮箱 ,2024年04期
  • 【分类号】R9;TP18
  • 【下载频次】8
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