UMR 1253, iBrain, Inserm, 37000 Tours, France; University of Tours, 37000 Tours, France.
University of Tours, 37000 Tours, France; UMR 1100, CEPR, Inserm, 37000 Tours, France.
Pharmacol Ther. 2022 May;233:108022. doi: 10.1016/j.pharmthera.2021.108022. Epub 2021 Oct 20.
Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021-2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered intravenously, alternative delivery routes have emerged to improve antibody therapeutic index and patient comfort. A major hurdle for antibody delivery and efficacy as well as the development of alternative administration routes, is to understand the different natural and pathological barriers that antibodies face as soon as they enter the body up to the moment they bind to their target antigen. In this review, we discuss the well-known and more under-investigated extracellular and cellular barriers faced by antibodies. We also discuss some of the strategies developed in the recent years to overcome these barriers and increase antibody delivery to its site of action. A better understanding of the biological barriers that antibodies have to face will allow the optimization of antibody delivery near its target. This opens the way to the development of improved therapy with less systemic side effects and increased patients' adherence to the treatment.
抗体药物已成为治疗药物的主要类别，在欧盟或美国，有超过 120 种重组抗体获得批准或正在审查中。由于全球对 SARS-CoV2 大流行的非凡反应以及公开披露的 100 多种抗 SARS-CoV2 抗体，该治疗类别经历了显著扩张，并预计在 2021-2022 年加速。主要通过静脉内给药，出现了替代给药途径，以提高抗体治疗指数和患者舒适度。抗体输送和疗效以及替代给药途径开发的主要障碍是，一旦抗体进入体内，直到它们与目标抗原结合，就要了解抗体所面临的不同自然和病理屏障。在这篇综述中，我们讨论了抗体所面临的众所周知和研究较少的细胞外和细胞屏障。我们还讨论了近年来为克服这些障碍和增加抗体向作用部位输送而开发的一些策略。更好地了解抗体必须面对的生物学障碍将允许在其目标附近优化抗体输送。这为开发副作用更少的改良疗法和提高患者对治疗的依从性开辟了道路。
