ArticleFrontiers in immunology2018
Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Potency-optimized CD28-activating bispecific antibody for the targeted treatment of Nectin-4 positive cancers.Journal for immunotherapy of cancer · 2025Article
- Single-chain antibody gene therapy strategy based on high-throughput screening triggers sustained antiviral activity in the body.Journal of virology · 2025Article
- An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies.Antibodies (Basel, Switzerland) · 2024Article
- Anti-BCMA novel therapies for multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Humanized single-domain antibody targeting HER2 enhances function of chimeric antigen receptor T cells.Frontiers in immunology · 2023Article
- A T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer.Oncoimmunology · 2022Article
- Attenuating CD3 affinity in a PSMAxCD3 bispecific antibody enables killing of prostate tumor cells with reduced cytokine release.Journal for immunotherapy of cancer · 2021Article
- A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells.Scientific reports · 2021Article
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- CD38 ecto-enzyme in immune cells is induced during aging and regulates NADNature metabolism · 2020Article
- A One-Step Process for the Construction of Phage Display scFv and VHH Libraries.Molecular biotechnology · 2020Article
- Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains.Nature communications · 2020Article
- RNase H-dependent PCR enables highly specific amplification of antibody variable domains from single B-cells.PloS one · 2020Article
- Bispecific antibodies: a mechanistic review of the pipeline.Nature reviews. Drug discovery · 2019Review
- Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma.Frontiers in immunology · 2019Article
- Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies.Frontiers in immunology · 2018Article
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22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.