a Bio-Rad, Antibody Division , Puchheim , Germany.
MAbs. 2019 Jan;11(1):178-190. doi: 10.1080/19420862.2018.1538723. Epub 2018 Dec 5.
Anti-idiotypic antibodies play an important role in pre-clinical and clinical development of therapeutic antibodies, where they are used for pharmacokinetic studies and for the development of immunogenicity assays. By using an antibody phage display library in combination with guided in vitro selection against various marketed drugs, we generated antibodies that recognize the drug only when bound to its target. We have named such specificities Type 3, to distinguish them from the anti-idiotypic antibodies that specifically detect free antibody drug or total drug. We describe the generation and characterization of such reagents for the development of ligand binding assays for drug quantification. We also show how these Type 3 antibodies can be used to develop very specific and sensitive assays that avoid the bridging format. Abbreviations: BAP: bacterial alkaline phosphatase; CDR: complementarity-determining regions in VH or VL; Fab: antigen-binding fragment of an antibody; HRP: horseradish peroxidase; HuCAL®: Human Combinatorial Antibody Libraries; IgG: immunoglobulin G; LBA: ligand binding assay; LOQ: limit of quantitation; NHS: normal human serum; PK: pharmacokinetics; VH: variable region of the heavy chain of an antibody; VL: variable region of the light chain of an antibody.
抗独特型抗体在治疗性抗体的临床前和临床开发中起着重要作用，用于药代动力学研究和免疫原性检测的开发。通过使用抗体噬菌体展示文库并结合针对各种市售药物的体外导向选择，我们生成了仅在与靶标结合时识别药物的抗体。我们将这种特异性命名为 3 型，以将其与专门检测游离抗体药物或总药物的抗独特型抗体区分开来。我们描述了这些试剂的产生和特性，用于开发用于药物定量的配体结合测定法。我们还展示了如何使用这些 3 型抗体来开发非常特异和灵敏的测定法，避免桥连格式。缩写：BAP：细菌碱性磷酸酶；CDR：重链或轻链的互补决定区；Fab：抗体的抗原结合片段；HRP：辣根过氧化物酶；HuCAL®：人组合抗体文库；IgG：免疫球蛋白 G；LBA：配体结合测定法；LOQ：定量下限；NHS：正常人类血清；PK：药代动力学；VH：抗体重链的可变区；VL：抗体轻链的可变区。
