Phage display is a powerful tool in identifying specific antibody fragment binding to the target. Several strategies can be used to screen out a specific Fab from the phage library that binds to an antigen; it may be performed on immobilized targeted molecule, on the intact cells, or by other strategies. Antibodies with properties of recognizing tumor cell surface receptors in native conformation and ability to internalize to tumor cells through receptor binding are ideal carriers for targeted immuno-chemo and/or immuno-radiation therapy. This chapter describes a unique bio-panning method to screen out a Fab fragment against human epithelial growth factor receptor (EGFR) from a naive human Fab phage library for potential targeted therapeutic application on EGFR overexpressed cancers.
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Enhancement of plasma kallikrein specificity of antitrypsin variants identified by phage display and partial reversion.
BMC Biotechnol
March 2025
Department of Pathology and Molecular Medicine HSC 4H19, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
Background: The naturally occurring variant Alpha-1 Antitrypsin M358R (AAT M358R), modified at the P1 position of the reactive center loop (RCL), shifts its inhibitory protease target from neutrophil elastase to multiple coagulation and contact proteases, including activated plasma kallikrein (Pka; KLKB1). Our aim was to increase the specificity of AAT M358R for Pka as a potential novel therapeutic agent to treat pathological swelling arising from elevated Pka levels in patients with Hereditary Angioedema.
Results: Two AAT M358R T7Select phage display libraries randomized at RCL positions P7-P3 and P2-P3' were iteratively probed with Pka.
Rational design of cyclic peptides, with an emphasis on bicyclic peptides.
Curr Opin Struct Biol
March 2025
BicycleTx Ltd, Blocks A&B, Portway Building, Granta Park, Great Abington, Cambridge, CB21 6GS, UK.
Macrocyclic peptides are a promising chemotype for drug discovery, given their attractive properties of proteolytic stability, bioavailability and the ability to inhibit protein-protein interactions. Approaches to the generation of macrocyclic peptides include optimisation of hits from library screening; de novo design from known ligands and antibody paratopes or protein-protein interactions; constraint of linear peptides to afford beneficial properties of macrocycles; and novel approaches to cyclisation. We describe the recent literature and exemplify these approaches in the design of peptide macrocycles, and the benefits of incorporating computational and structure-guided approaches into compound design and optimisation.
View Article and Find Full Text PDFBotulinum neurotoxin (BoNT) is a highly lethal toxin produced by the anaerobic bacterium Clostridium botulinum, which leads to nerve paralysis following poisoning. At present, there is no specific drug officially approved. Antibodies, particularly single-domain antibodies, represent safe and effective candidates for specific drugs against BoNT.
View Article and Find Full Text PDFApplication of phage surface display for the identification of Eu-binding peptides.
Front Bioeng Biotechnol
February 2025
Biotechnology Division, Helmholtz-Zentrum Dresden-Rossendorf, Helmholtz Institute Freiberg for Resource Technology, Dresden, Germany.
Europium as one of the rare earth elements (REE) has outstanding properties in terms of its application for high-tech and renewable energy products. The high supply risk of REE, coupled with their low recovery rates from secondary sources, necessitates innovative recycling approaches. We introduce a phage display-based peptide biosorbent recycling technology that offers a cost-effective and environmentally friendly solution for recovering metal ions, supporting circular economy goals.
View Article and Find Full Text PDF[Construction of a human anti-SARS-CoV-2 scFv library and identification of broad-spectrum neutralizing antibodies].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
February 2025
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. *Corresponding authors, E-mail:
Objective To construct a library of human-derived anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) single-chain variable fragments (scFv) and screen for broad-spectrum neutralizing antibodies to identify candidate molecules for the development of diagnostic and therapeutic agents. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of patients who had recovered from novel coronavirus infection. Total RNA was extracted from these PBMCs and reverse transcribed into cDNA, which was used as a template for constructing a human anti-SARS-CoV-2 scFv library.
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