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探索前沿领域:治疗性抗体设计与分析中计算方法的全面概述

Navigating the landscape: A comprehensive overview of computational approaches in therapeutic antibody design and analysis.

作者信息

Yadav Amar Jeet, Bhagat Khushboo, Sharma Akshit, Padhi Aditya K

机构信息

Laboratory for Computational Biology & Biomolecular Design, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, Uttar Pradesh, India.

Laboratory for Computational Biology & Biomolecular Design, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, Uttar Pradesh, India.

出版信息

Adv Protein Chem Struct Biol. 2025;144:33-76. doi: 10.1016/bs.apcsb.2024.10.011. Epub 2025 Jan 31.

Abstract

Immunotherapy, harnessing components like antibodies, cells, and cytokines, has become a cornerstone in treating diseases such as cancer and autoimmune disorders. Therapeutic antibodies, in particular, have transformed modern medicine, providing a targeted approach that destroys disease-causing cells while sparing healthy tissues, thereby reducing the side effects commonly associated with chemotherapy. Beyond oncology, these antibodies also hold promise in addressing chronic infections where conventional therapeutics may fall short. However, antibodies identified through in vivo or in vitro methods often require extensive engineering to enhance their therapeutic potential. This optimization process, aimed at improving affinity, specificity, and reducing immunogenicity, is both challenging and costly, often involving trade-offs between critical properties. Traditional methods of antibody development, such as hybridoma technology and display techniques, are resource-intensive and time-consuming. In contrast, computational approaches offer a faster, more efficient alternative, enabling the precise design and analysis of therapeutic antibodies. These methods include sequence and structural bioinformatics approaches, next-generation sequencing-based data mining, machine learning algorithms, systems biology, immuno-informatics, and integrative approaches. These approaches are advancing the field by providing new insights and enhancing the accuracy of antibody design and analysis. In conclusion, computational approaches are essential in the development of therapeutic antibodies, significantly improving the precision and speed of discovery, optimization, and validation. Integrating these methods with experimental approaches accelerates therapeutic antibody development, paving the way for innovative strategies and treatments for various diseases ranging from cancers to autoimmune and infectious diseases.

摘要

免疫疗法利用抗体、细胞和细胞因子等成分,已成为治疗癌症和自身免疫性疾病等疾病的基石。特别是治疗性抗体,已经改变了现代医学,提供了一种靶向方法,能够在不损伤健康组织的情况下破坏致病细胞,从而减少了通常与化疗相关的副作用。除了肿瘤学领域,这些抗体在解决传统疗法可能失效的慢性感染方面也具有前景。然而,通过体内或体外方法鉴定的抗体通常需要大量工程改造来增强其治疗潜力。这个旨在提高亲和力、特异性并降低免疫原性的优化过程既具有挑战性又成本高昂,常常需要在关键特性之间进行权衡。传统的抗体开发方法,如杂交瘤技术和展示技术,资源密集且耗时。相比之下,计算方法提供了一种更快、更高效的替代方案,能够实现治疗性抗体的精确设计和分析。这些方法包括序列和结构生物信息学方法、基于下一代测序的数据挖掘、机器学习算法、系统生物学、免疫信息学以及综合方法。这些方法通过提供新的见解并提高抗体设计和分析的准确性,推动了该领域的发展。总之,计算方法在治疗性抗体的开发中至关重要,显著提高了发现、优化和验证的精度和速度。将这些方法与实验方法相结合,加速了治疗性抗体的开发,为从癌症到自身免疫性疾病和传染病等各种疾病的创新策略和治疗方法铺平了道路。

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