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单克隆抗体五十年:抗体疗法的过去、现在与未来

英文原题:Fifty years of monoclonals: the past, present and future of antibody therapeutics.

PubMed 2025/08/07(内容时间) Nat Rev Immunol Q1 · IF 47.1(JCR 2025)

研究概要

1975年,Köhler和Milstein发明了杂交瘤技术,用于生成具有预定抗原结合特异性的鼠源单克隆抗体。

中文摘要

1975年,Köhler和Milstein发明了杂交瘤技术,用于生成具有预定抗原结合特异性的鼠源单克隆抗体。单克隆抗体的变革性影响体现在其作为生物医学研究试剂的无处不在的应用,以及全球至少212种抗体治疗药物获得批准,迄今为止已治疗数千万患者。抗体技术的进步,如人源化和稳健的人抗体生成方法,减轻了鼠源抗体作为治疗药物的主要局限性。这些技术与生物制造方面的进展相结合,帮助开启了抗体治疗药物的现代时代。除了IgG之外,抗体治疗药物已发展为多种替代形式,包括双特异性抗体和抗体-药物偶联物。此外,抗体片段已被开发为独立治疗药物以及用于靶向细胞治疗,特别是CAR-T 细胞。这些抗体技术的进步,加上实现皮下递送的创新,改善了许多患者抗体治疗的治疗获益和便利性。这一概念在此通过针对人表皮生长因子受体2(HER2)+癌症的多代抗体治疗药物以及针对血液系统癌症和免疫疾病的B细胞靶向治疗得到说明。最后,我们简要展望了抗体治疗药物众多有前景的未来方向中的一些,包括应用人工智能进行抗体识别和多参数优化。

展开英文摘要原文

In 1975, Köhler and Milstein invented hybridoma technology for the generation of murine monoclonal antibodies with predetermined antigen-binding specificity. The transformative impact of monoclonal antibodies is demonstrated by their ubiquitous use as biomedical research reagents and the worldwide approval of at least 212 antibody therapeutics with tens of millions of patients treated to date. Advances in antibody technologies, such as humanization and robust methods for human antibody generation, mitigated the major limitations of murine antibodies as therapeutics. These technologies, combined with progress in biomanufacturing, helped to launch this modern era of antibody therapeutics. Beyond IgG, antibody therapeutics have blossomed into multiple alternative formats, including bispecific antibodies and antibody-drug conjugates. Additionally, antibody fragments have been developed as stand-alone therapeutics and to target cell therapies, notably chimeric antigen receptor T cells. These advances in antibody technologies, plus innovation enabling subcutaneous delivery, have improved the therapeutic benefits and convenience of antibody treatment for many patients. This concept is illustrated here by multiple generations of antibody therapeutics for human epidermal growth factor receptor 2 (HER2) + cancers and B cell-targeted therapies for haematological cancers and immunological diseases. Finally, we opine briefly on some of the many promising future directions with antibody therapeutics, including the application of artificial intelligence for antibody identification and multi-parameter optimization.

论文信息

作者
Chan AC、Martyn GD、Carter PJ
第一作者单位
Department of Research Biology, Genentech, South San Francisco, CA, USA. acc@gene.com.United States
通讯作者单位
Department of Antibody Engineering, Genentech, South San Francisco, CA, USA. pjc@gene.com.United States
文献类型
历史回顾
期刊
Nature reviews. Immunology2025 Oct
原文标识
PubMed 40775487 · DOI 10.1038/s41577-025-01207-9