High Affinity Maturated Human Antibodies from Naïve and Synthetic Antibody Repertoires

Lim, Chia Chiu; Choong, Yee Siew; Lim, Theam Soon

doi:10.5772/intechopen.71664

Cited by 3 publications

(3 citation statements)

References 131 publications

(162 reference statements)

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“…The naïve human antibody libraries have been constructed using human B cells of non-immunized or healthy donors [ 48 ]. The antibodies isolated from naïve human antibody libraries may often exhibit lower affinities because the antibody repertoire does not undergo in vivo affinity maturation to produce higher-affinity antibodies [ 48 , 49 ]. In the present study, we assert that the library we have developed is a high-quality human antibody library with large and diverse repertoires.…”

Section: Discussionmentioning

confidence: 99%

Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library

Choi

Yang

Shin

et al. 2023

IJMS

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Antibody phage display is a key technology for the discovery and development of target-specific monoclonal antibodies (mAbs) for use in research, diagnostics, and therapy. The construction of a high-quality antibody library, with larger and more diverse antibody repertoires, is essential for the successful development of phage display-derived mAbs. In this study, a large human combinatorial single-chain variable fragment library (1.5 × 1011 colonies) was constructed from Epstein–Barr virus-infected human peripheral blood mononuclear cells stimulated with a combination of two of the activators of human B cells, the Toll-like receptor 7/8 agonist R848 and interleukin-2. Next-generation sequencing analysis with approximately 1.9 × 106 and 2.7 × 106 full-length sequences of heavy chain variable (VH) and κ light chain variable (Vκ) domains, respectively, revealed that the library consists of unique VH (approximately 94%) and Vκ (approximately 91%) sequences with greater diversity than germline sequences. Lastly, multiple unique mAbs with high affinity and broad cross-species reactivity could be isolated from the library against two therapeutically relevant target antigens, validating the library quality. These findings suggest that the novel antibody library we have developed may be useful for the rapid development of target-specific phage display-derived recombinant human mAbs for use in therapeutic and diagnostic applications.

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Section: Discussionmentioning

confidence: 99%

Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library

Choi

Yang

Shin

et al. 2023

IJMS

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“…Biological display systems have been systematically developed for more than 30 years and have been broadly used for high-throughput ligand selection and other fields (Figure 2) [16]. With gene recombinant technologies, the structure of natural ligands can be conveniently imitated and reshaped by incorporating functional tags, groups, and linkers.…”

Section: High-throughput Screening Using Biological Display Systemsmentioning

confidence: 99%

High‐throughput screening and biological display technology: Applications in molecular imaging

2023

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Molecular imaging plays important roles in many fields, including disease diagnosis, therapeutic efficacy evaluation, intraoperative imaging guidance, drug metabolism monitoring, and patient selection for appropriate treatment. As a key component, the targeting ligand determines the specificity, affinity, and in vivo performance of molecular imaging probes. In this review, high‐throughput screening and biological display platforms for the discovery of ligands applicable to molecular imaging are briefly reviewed. Basic information on ligand development for molecular imaging is first introduced, followed by a presentation of various selection platforms and typical or iterative cases. The features, advantages, limitations, and application scope of screening and display platforms are compared and discussed. Last, a basic selection strategy and a perspective for protein‐based ligands are provided.

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“…Antibody libraries can be distinguished by the source of antibody genes used for display. This ranges from naïve (healthy individuals), immune (infected or immunized individuals), synthetic (chemically synthesized) and semi-synthetic (a mixture of natural immune and chemically synthesized genes) libraries [14][15][16]. The development of human antibody libraries requires B-cells obtained from human donors which sometimes represents a bottleneck due to the specific characteristics of the samples needed such as source of the B-cells, and the strict regulation in terms of human biological samples usage in research.…”

Section: Introductionmentioning

confidence: 99%

Infectious disease antibodies for biomedical applications: A mini review of immune antibody phage library repertoire

Lai

Lim

2020

International Journal of Biological Macromolecules

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Antibody phage display is regarded as a critical tool for the development of monoclonal antibodies for infectious diseases. The different classes of antibody libraries are classified based on the source of repertoire used to generate the libraries. Immune antibody libraries are generated from disease infected host or immunization against an infectious agent. Antibodies derived from immune libraries are distinct from those derived from naïve libraries as the host's in vivo immune mechanisms shape the antibody repertoire to yield high affinity antibodies. As the immune system is constantly evolving in accordance to the health state of an individual, immune libraries can offer more than just infection-specific antibodies but also antibodies derived from the memory B-cells much like naïve libraries. The combinatorial nature of the gene cloning process would give rise to a combination of natural and unnatural antibody gene pairings in the immune library. These factors have a profound impact on the coverage of immune antibody libraries to target both disease-specific and non-disease specific antigens. This review looks at the diverse nature of antibody responses for immune library generation and discusses the extended potential of a disease-specified immune library in the context of phage display.

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High Affinity Maturated Human Antibodies from Naïve and Synthetic Antibody Repertoires

Abstract: Recombinant human antibody technology has been the cornerstone of the uprising of biologics in the pharmaceutical industry.

Cited by 3 publications

References 131 publications

Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library

Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library

High‐throughput screening and biological display technology: Applications in molecular imaging

Infectious disease antibodies for biomedical applications: A mini review of immune antibody phage library repertoire

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