Ueberberg S, Schneider S
Medical Department 1, Division of Endocrinology and Metabolism, University Hospital Bergmannsheil, Ruhr-University of Bochum, 44789 Bochum, Germany.
Regul Pept. 2010 Feb 25;160(1-3):1-8. doi: 10.1016/j.regpep.2009.11.017. Epub 2009 Dec 1.
Phage display technology is a powerful approach for the generation of peptides and antibodies that target specific organ- or tumor-structures. By applying this approach to rats in vivo or freshly isolated rat islets in vitro, we have recently reported the successful isolation of internalizing single-chain antibodies (SCA-antibodies), which are highly specific for the endocrine-cells of a pancreatic islet (either beta- or alpha-cells) both in rodents and in humans. Moreover, others have reported peptides targeting specifically the vascular endothelium of normal or pre-malignant islets or advanced islet-cell tumors. The features of these antibodies and peptides are compatible with a potential use for in vivo delivery of molecular cargos (e.g. imaging agents and therapeutics). Therefore, this article reviews the principles of phage display, provides an overview about agents either specific for the endocrine-cells or the vascular endothelium of islets, discusses methododical key elements for the generation of these ligands and highlights remaining questions and potential future perspectives.
噬菌体展示技术是一种用于生成靶向特定器官或肿瘤结构的肽和抗体的强大方法。通过将这种方法应用于体内的大鼠或体外新鲜分离的大鼠胰岛,我们最近报道了成功分离出内化单链抗体(SCA抗体),该抗体在啮齿动物和人类中对胰岛的内分泌细胞(β细胞或α细胞)具有高度特异性。此外,其他人还报道了特异性靶向正常或癌前胰岛或晚期胰岛细胞瘤血管内皮的肽。这些抗体和肽的特性与体内递送分子货物(如成像剂和治疗剂)的潜在用途相兼容。因此,本文回顾了噬菌体展示的原理,概述了对胰岛内分泌细胞或血管内皮具有特异性的试剂,讨论了生成这些配体的方法学关键要素,并强调了剩余的问题和潜在的未来前景。