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从噬菌体文库中进行高通量单克隆抗体发现:挑战当前临床前流程以跟上单克隆抗体需求的增长步伐。

High-Throughput Monoclonal Antibody Discovery from Phage Libraries: Challenging the Current Preclinical Pipeline to Keep the Pace with the Increasing mAb Demand.

作者信息

Zambrano Nicola, Froechlich Guendalina, Lazarevic Dejan, Passariello Margherita, Nicosia Alfredo, De Lorenzo Claudia, Morelli Marco J, Sasso Emanuele

机构信息

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy.

CEINGE-Biotecnologie Avanzate s.c. a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.

出版信息

Cancers (Basel). 2022 Mar 4;14(5):1325. doi: 10.3390/cancers14051325.

DOI:10.3390/cancers14051325
PMID:35267633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8909429/
Abstract

Monoclonal antibodies are among the most powerful therapeutics in modern medicine. Since the approval of the first therapeutic antibody in 1986, monoclonal antibodies keep holding great expectations for application in a range of clinical indications, highlighting the need to provide timely and sustainable access to powerful screening options. However, their application in the past has been limited by time-consuming and expensive steps of discovery and production. The screening of antibody repertoires is a laborious step; however, the implementation of next-generation sequencing-guided screening of single-chain antibody fragments has now largely overcome this issue. This review provides a detailed overview of the current strategies for the identification of monoclonal antibodies from phage display-based libraries. We also discuss the challenges and the possible solutions to improve the limiting selection and screening steps, in order to keep pace with the increasing demand for monoclonal antibodies.

摘要

单克隆抗体是现代医学中最强大的治疗手段之一。自1986年首个治疗性抗体获批以来,单克隆抗体在一系列临床适应症中的应用一直备受期待,这凸显了及时且持续地提供强大筛选选项的必要性。然而,它们过去的应用受到发现和生产过程中耗时且昂贵步骤的限制。抗体库的筛选是一个费力的步骤;不过,基于下一代测序的单链抗体片段筛选的实施现已在很大程度上克服了这个问题。本综述详细概述了从基于噬菌体展示的文库中鉴定单克隆抗体的当前策略。我们还讨论了改进有限的选择和筛选步骤的挑战及可能的解决方案,以便跟上对单克隆抗体日益增长的需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/e8e48fb4baa7/cancers-14-01325-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/70ac38cd175e/cancers-14-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/b7fc165dc90d/cancers-14-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/08114359af06/cancers-14-01325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/775798d04495/cancers-14-01325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/1e279f2d870e/cancers-14-01325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/ab6995ac4e5b/cancers-14-01325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/e8e48fb4baa7/cancers-14-01325-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/70ac38cd175e/cancers-14-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/b7fc165dc90d/cancers-14-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/08114359af06/cancers-14-01325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/775798d04495/cancers-14-01325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/1e279f2d870e/cancers-14-01325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/ab6995ac4e5b/cancers-14-01325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b04/8909429/e8e48fb4baa7/cancers-14-01325-g007.jpg

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SINEUPs: a novel toolbox for RNA therapeutics.SINEUPs:一种新型的 RNA 治疗工具。
Selection of Affibody Affinity Proteins from Phagemid Libraries.
从噬菌体展示文库中筛选亲和体结合蛋白。
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A Novel Strategy for Screening Tumor-Specific Variable Domain of Heavy-Chain Antibodies.一种筛选重链抗体肿瘤特异性可变结构域的新策略。
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Production of a Ribosome-Displayed Mouse scFv Antibody Against CD133, Analysis of Its Molecular Docking, and Molecular Dynamic Simulations of Their Interactions.核糖体展示技术筛选抗 CD133 单链抗体及其分子对接和分子动力学模拟分析
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