Janssen Biotherapeutics, The Janssen Pharmaceutical Companies of Johnson & Johnson, 1400 McKean Road, Spring House, PA 19477, USA.
Janssen Biotherapeutics, The Janssen Pharmaceutical Companies of Johnson & Johnson, 1400 McKean Road, Spring House, PA 19477, USA.
Trends Biotechnol. 2021 Mar;39(3):298-310. doi: 10.1016/j.tibtech.2020.07.003. Epub 2020 Aug 14.
Intracellular delivery of therapeutic antibodies is highly desirable but remains a challenge for biomedical research and the pharmaceutical industry. Approximately two-thirds of disease-associated targets are found inside the cell. Difficulty blocking these targets with available drugs creates a need for technology to deliver highly specific therapeutic antibodies intracellularly. Historically, antibodies have not been believed to traverse the cell membrane and neutralize intracellular targets. Emerging evidence has revealed that anti-DNA autoantibodies found in systemic lupus erythematosus (SLE) patients can penetrate inside the cell. Harnessing this technology has the potential to accelerate the development of drugs against intracellular targets. Here, we dissect the mechanisms of the intracellular localization of SLE antibodies and discuss how to apply these insights to engineer successful cell-penetrating antibody drugs.
细胞内递呈治疗性抗体是非常理想的，但对于生物医药研究和制药行业来说仍然是一个挑战。大约三分之二的与疾病相关的靶标存在于细胞内。由于现有的药物难以阻断这些靶标，因此需要技术将高度特异性的治疗性抗体递送至细胞内。从历史上看，抗体被认为不能穿过细胞膜并中和细胞内的靶标。新出现的证据表明，在系统性红斑狼疮（SLE）患者中发现的抗 DNA 自身抗体可以穿透细胞内部。利用这项技术有可能加速针对细胞内靶标的药物的开发。在这里，我们剖析了 SLE 抗体的细胞内定位的机制，并讨论了如何将这些见解应用于工程成功的穿透细胞的抗体药物。
