Evolution of phage display libraries for therapeutic antibody discovery

mAbs, Journal Year: 2023, Volume and Issue: 15(1)

Published: May 24, 2023

Monoclonal antibodies (mAbs) and their derivatives have emerged as one of the most important classes biotherapeutics in recent decades. The success mAb is due to high versatility, target specificity, excellent clinical safety profile, efficacy. Antibody discovery, upstream stage antibody development pipeline, plays a pivotal role determination outcome an product. Phage display technology, originally developed for peptide directed evolution, has been extensively applied discovery fully human its unprecedented advantages. value phage technology proven by number approved mAbs, including several top-selling drugs, derived from technology. Since was first established over 30 years ago, platforms generate mAbs targeting difficult-to-target antigens tackle drawbacks present vivo approaches. More recently, new generation libraries optimized with "drug-like" properties. This review will summarize principles design three generations libraries.

Language: Английский

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Exploring protein-protein interactions at the proteome level

Structure, Journal Year: 2022, Volume and Issue: 30(4), P. 462 - 475

Published: Feb. 25, 2022

Language: Английский

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Aspects of Phage-Based Vaccines for Protein and Epitope Immunization

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 436 - 436

Published: Feb. 14, 2023

Because vaccine development is a difficult process, this study reviews aspects of phages as delivery vehicles through literature search. The results demonstrated that because have adjuvant properties and are safe for humans animals, they an excellent tool protein epitope immunization. phage genome can easily be manipulated to display antigens or create DNA vaccines. Additionally, easy produce on large scale, which lowers their manufacturing costs. They stable under various conditions, facilitate transport storage. However, no medicine regulatory agency has yet authorized phage-based vaccines despite the considerable preclinical data confirming benefits. skeptical perspective should overcome encounter bacteriophages in environment all time without suffering adverse effects. lack clinical trials, endotoxin contamination, composition, long-term negative effects some obstacles preventing prospects promising trials; been food additive avoid contamination approved emergency use therapy against difficult-to-treat antibiotic-resistant bacteria. Therefore, encourages

Language: Английский

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Multivalent protein-drug conjugates – An emerging strategy for the upgraded precision and efficiency of drug delivery to cancer cells

Biotechnology Advances, Journal Year: 2023, Volume and Issue: 67, P. 108213 - 108213

Published: July 13, 2023

With almost 20 million new cases per year, cancer constitutes one of the most important challenges for public health systems. Unlike traditional chemotherapy, targeted anti-cancer strategies employ sophisticated therapeutics to precisely identify and attack cells, limiting impact drugs on healthy cells thereby minimizing unwanted side effects therapy. Protein drug conjugates (PDCs) are a rapidly growing group therapeutics, composed cancer-recognition factor covalently coupled cytotoxic drug. Several PDCs, mainly in form antibody-drug (ADCs) that monoclonal antibodies as molecules, used clinic many PDCs currently clinical trials. Highly selective, strong stable interaction PDC with tumor marker, combined efficient, rapid endocytosis receptor/PDC complex its subsequent effective delivery lysosomes, is critical efficacy therapy PDCs. However, bivalent architecture contemporary not optimal receptor recognition or internalization. In this review, we focus multivalent which represent evolving highly promising overcome limitations current enhancing precision efficiency cells. We present an expanding set protein scaffolds generate that, addition folding into well-defined molecular structures, enable site-specific conjugation ensure homogeneity. provide overview architectures developed date, emphasizing their treatment various cancers.

Language: Английский

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How can we discover developable antibody-based biotherapeutics?

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 7, 2023

Antibody-based biotherapeutics have emerged as a successful class of pharmaceuticals despite significant challenges and risks to their discovery development. This review discusses the most frequently encountered hurdles in research development (R&D) antibody-based proposes conceptual framework called biopharmaceutical informatics. Our vision advocates for syncretic use computation experimentation at every stage biologic drug discovery, considering developability (manufacturability, safety, efficacy, pharmacology) potential candidates from earliest stages phase. The computational advances recent years allow more precise formulation disease concepts, rapid identification, validation targets suitable therapeutic intervention that can agonize or antagonize them. Furthermore, methods

Language: Английский

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Review of phage display: A jack-of-all-trades and master of most biomolecule display

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 256, P. 128455 - 128455

Published: Nov. 25, 2023

Language: Английский

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Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(3), P. 345 - 345

Published: Feb. 29, 2024

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence adult normal tissues benign lesions. This unique pattern positions FAP as prospective biomarker for targeted tumor radiodiagnosis therapy. The advent of FAP-based radiotheranostics anticipated to revolutionize cancer management. Among various types ligands, peptides antibodies have shown advantages over small molecules, exemplifying prolonged retention human volunteers. Within scope, this review summarizes the recent research progress radiopharmaceuticals based on imaging Additionally, it incorporates insights from studies, providing valuable perspectives clinical utility FAP-targeted radiopharmaceuticals.

Language: Английский

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Disulfide-constrained peptide scaffolds enable a robust peptide-therapeutic discovery platform

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(3), P. e0300135 - e0300135

Published: March 28, 2024

Peptides present an alternative modality to immunoglobulin domains or small molecules for developing therapeutics either agonize antagonize cellular pathways associated with diseases. However, peptides often suffer from poor chemical and physical stability, limiting their therapeutic potential. Disulfide-constrained (DCP) are naturally occurring possess numerous desirable properties, such as high that qualify them drug-like scaffolds peptide therapeutics. DCPs contain loop regions protruding the core of molecule amenable engineering via direct evolution by use phage display technology. In this study, we have established a robust platform discovery using various scaffolds. We created diverse libraries comprising seven different DCP scaffolds, resulting in overall diversity 2 x 1011. The effectiveness functional hit has been extensively evaluated, demonstrating rate comparable synthetic antibody libraries. By utilizing chemically synthesized vitro folded derived selections displayed libraries, successfully generated inhibitors targeting HtrA1 protease. Through affinity maturation strategies, transformed initially weak binders against Notch2 micromolar Kd values high-affinity ligands nanomolar range. This process highlights viable hit-to-lead progression. Overall, our holds significant potential greatly enhance

Language: Английский

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The Use of Bacteriophages in Biotechnology and Recent Insights into Proteomics

Antibiotics, Journal Year: 2022, Volume and Issue: 11(5), P. 653 - 653

Published: May 13, 2022

Phages have certain features, such as their ability to form protein–protein interactions, that make them good candidates for use in a variety of beneficial applications, human or animal health, industry, food science, safety, and agriculture. It is essential identify characterize the proteins produced by particular phages order these viruses functional processes, bacterial detection, vehicles drug delivery, vaccine development, combat multidrug resistant infections. Furthermore, can also play major role design cheap stable sensors well diagnostic assays either specifically specific compounds detect bacteria. This article reviews recently developed phage-based techniques, recombinant tempered phages, phage display amplification-based detection. encompasses application capture elements, biosensors bioreceptors, with special emphasis on novel bacteriophage-based mass spectrometry (MS) applications.

Language: Английский

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How to Tackle Bacteriophages: The Review of Approaches with Mechanistic Insight

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4447 - 4447

Published: Feb. 23, 2023

Bacteriophage-based applications have a renaissance today, increasingly marking their use in industry, medicine, food processing, biotechnology, and more. However, phages are considered resistant to various harsh environmental conditions; besides, they characterized by high intra-group variability. Phage-related contaminations may therefore pose new challenges the future due wider of industry health care. Therefore, this review, we summarize current knowledge bacteriophage disinfection methods, as well highlight technologies approaches. We discuss need for systematic solutions improve control, taking into account structural diversity.

Language: Английский

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