ArticleProceedings of the National Academy of Sciences of the United States of America2015
Augmented Binary Substitution: Single-pass CDR germ-lining and stabilization of therapeutic antibodies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- The Evolution of Artificial Intelligence in Antibody Design: From Structure-Based Engineering to Generative Models.Antibodies (Basel, Switzerland) · 2026Review
- A humanized neutralizing antibody protects against human adenovirus type 7 infection in humanized desmoglein-2 and CD46 double-receptor transgenic mice.Virology journal · 2024Article
- Characterization and root cause analysis of immunogenicity to pasotuxizumab (AMG 212), a prostate-specific membrane antigen-targeting bispecific T-cell engager therapy.Frontiers in immunology · 2023Article
- How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023Review
- Crystal structure of ultra-humanized anti-pTau Fab reveals how germline substitutions humanize CDRs without loss of binding'.Scientific reports · 2022Article
- Optimization of therapeutic antibodies by predicting antigen specificity from antibody sequence via deep learning.Nature biomedical engineering · 2021Article
- Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives.International immunopharmacology · 2020Review
- Affinity improvement of the fully human anti‑TSLP recombinant antibody.Molecular medicine reports · 2020Article
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- Phage Display: A Powerful Technology for the Generation of High-Specificity Affinity Reagents from Alternative Immune Sources.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy.Frontiers in immunology · 2017Review
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- High-efficiency antibody discovery achieved with multiplexed microscopy.Microscopy (Oxford, England) · 2016Article
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Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although humanized antibodies have been highly successful in the clinic, all current humanization techniques have potential limitations, such as: reliance on rodent hosts, immunogenicity due to high non-germ-line amino acid content, v-domain destabilization, expression and formulation issues. This study presents a technology that generates stable, soluble, ultrahumanized antibodies via single-step complementarity-determining region (CDR) germ-lining. For three antibodies from three separate key immune host species, binary substitution CDR cassettes were inserted into preferred human frameworks to form libraries in which only the parental or human germ-line destination residue was encoded at each position. The CDR-H3 in each case was also augmented with 1 ± 1 random substitution per clone. Each library was then screened for clones with restored antigen binding capacity. Lead ultrahumanized clones demonstrated high stability, with affinity and specificity equivalent to, or better than, the parental IgG. Critically, this was mainly achieved on germ-line frameworks by simultaneously subtracting up to 19 redundant non-germ-line residues in the CDRs. This process significantly lowered non-germ-line sequence content, minimized immunogenicity risk in the final molecules and provided a heat map for the essential non-germ-line CDR residue content of each antibody. The ABS technology therefore fully optimizes the clinical potential of antibodies from rodents and alternative immune hosts, rendering them indistinguishable from fully human in a simple, single-pass process.
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Registered trials
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.