» Articles » PMID: 37222232

Evolution of Phage Display Libraries for Therapeutic Antibody Discovery

Overview
Journal MAbs
Date 2023 May 24
PMID 37222232
Authors
Affiliations
Soon will be listed here.
Abstract

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

Citing Articles

Challenges and Insights in Absolute Quantification of Recombinant Therapeutic Antibodies by Mass Spectrometry: An Introductory Review.

Doring S, Weller M, Reinders Y, Konthur Z, Jaeger C Antibodies (Basel). 2025; 14(1.

PMID: 39846611 PMC: 11755444. DOI: 10.3390/antib14010003.


Engineering and Bio/Nanotechnological Applications of Virus Particles.

Mateu M, Valbuena A Subcell Biochem. 2024; 105:823-878.

PMID: 39738964 DOI: 10.1007/978-3-031-65187-8_22.


Heat-sterilizable antibody mimics designed on the cold shock protein scaffold from hyperthermophile Thermotoga maritima.

Amesaka H, Tachibana M, Hara M, Toya S, Nakagawa H, Matsumura H Protein Sci. 2024; 34(1):e70018.

PMID: 39724358 PMC: 11670304. DOI: 10.1002/pro.70018.


p-IgGen: a paired antibody generative language model.

Turnbull O, Oglic D, Croasdale-Wood R, Deane C Bioinformatics. 2024; 40(11).

PMID: 39520401 PMC: 11576349. DOI: 10.1093/bioinformatics/btae659.


Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.

Stephens A, Wilkinson T BioDrugs. 2024; 38(6):769-794.

PMID: 39453540 PMC: 11530565. DOI: 10.1007/s40259-024-00682-1.


References
1.
Fellouse F, Wiesmann C, Sidhu S . Synthetic antibodies from a four-amino-acid code: a dominant role for tyrosine in antigen recognition. Proc Natl Acad Sci U S A. 2004; 101(34):12467-72. PMC: 515084. DOI: 10.1073/pnas.0401786101. View

2.
Persson M, Caothien R, Burton D . Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. Proc Natl Acad Sci U S A. 1991; 88(6):2432-6. PMC: 51246. DOI: 10.1073/pnas.88.6.2432. View

3.
Bass S, Greene R, Wells J . Hormone phage: an enrichment method for variant proteins with altered binding properties. Proteins. 1990; 8(4):309-14. DOI: 10.1002/prot.340080405. View

4.
Jespers L, Roberts A, Mahler S, Winter G, Hoogenboom H . Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Biotechnology (N Y). 1994; 12(9):899-903. DOI: 10.1038/nbt0994-899. View

5.
Virnekas B, Ge L, Pluckthun A, Schneider K, Wellnhofer G, Moroney S . Trinucleotide phosphoramidites: ideal reagents for the synthesis of mixed oligonucleotides for random mutagenesis. Nucleic Acids Res. 1994; 22(25):5600-7. PMC: 310122. DOI: 10.1093/nar/22.25.5600. View