Chan Andrew C, Martyn Greg D, Carter Paul J
Department of Research Biology, Genentech, South San Francisco, CA, USA.
Department of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Nat Rev Immunol. 2025 Aug 7. doi: 10.1038/s41577-025-01207-9.
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.
1975年，科勒和米尔斯坦发明了杂交瘤技术，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广泛应用，以及全球范围内至少212种抗体疗法获得批准，迄今已有数千万患者接受治疗。抗体技术的进步，如人源化和强大的人源抗体生成方法，减轻了鼠源抗体作为治疗剂的主要局限性。这些技术与生物制造方面的进展相结合，助力开启了抗体治疗的现代时代。除了IgG，抗体疗法已发展出多种替代形式，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的治疗剂，并用于靶向细胞疗法，特别是嵌合抗原受体T细胞。抗体技术的这些进展，加上实现皮下给药的创新，改善了许多患者接受抗体治疗的疗效和便利性。本文通过用于治疗人表皮生长因子受体2（HER2）癌症的多代抗体疗法以及用于血液系统癌症和免疫疾病的B细胞靶向疗法对此概念进行了说明。最后，我们简要探讨了抗体治疗许多有前景的未来方向，包括人工智能在抗体识别和多参数优化中的应用。
