Department of Chemistry and iNano Interdisciplinary Nanoscience Centre, Aarhus University, Aarhus 8000, Denmark.
School of Chemical Engineering and Australian Centre for NanoMedicine (ACN), The University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia.
Adv Drug Deliv Rev. 2021 Mar;170:281-293. doi: 10.1016/j.addr.2021.01.010. Epub 2021 Jan 21.
A vast range of biomedical applications relies on the specificity of interactions between an antigen and its cognate receptor or antibody. This specificity can be highest when said antigen is a non-natural (synthetic) molecule introduced into a biological setting as a bio-orthogonal ligand. This review aims to present the development of this methodology from the early discovery of haptens a century ago to the recent clinical trials. We discuss such methodologies as antibody recruitment, artificial internalizing receptors and chemically induced dimerization, present the use of chimeric receptors and/or bispecific antibodies to achieve drug targeting and transcytosis, and illustrate how these platforms most impressively found use in the engineering of therapeutic cells such as the chimeric antigen receptor cells. This review aims to be of interest to a broad scientific audience and to spur the development of synthetic artificial ligands for biomedical applications.
广泛的生物医学应用依赖于抗原与其同源受体或抗体之间相互作用的特异性。当所述抗原是作为生物正交配体引入生物环境的非天然（合成）分子时，这种特异性可以最高。本综述旨在从一个世纪前半抗原的早期发现到最近的临床试验，介绍这种方法的发展。我们讨论了诸如抗体募集、人工内化受体和化学诱导二聚化等方法，介绍了使用嵌合受体和/或双特异性抗体来实现药物靶向和转胞运输，并说明了这些平台如何最令人印象深刻地用于工程治疗细胞，如嵌合抗原受体细胞。本综述旨在引起广大科学受众的兴趣，并激发用于生物医学应用的合成人工配体的发展。
