ArticlemAbs2015
A generic approach to engineer antibody pH-switches using combinatorial histidine scanning libraries and yeast display.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Breaking Biological Barriers: Engineering Nanocarriers for Efficient Drug and Gene Delivery through Nano-Bio Interfaces and Biophysical Design.Applied physics reviews · 2026Article
- Article
- Strategies to Screen and Evaluate Brain Targeting Antibodies Using an iPSC-Derived Blood-Brain Barrier Model.Antibodies (Basel, Switzerland) · 2025Article
- Engineered single chain variable fragments (scFvs) with improved pH-dependent kinetics for use in continuous biosensor applications.RSC advances · 2025Article
- pH-dependent dissociation from CTLA-4 in early endosomes improves both safety and antitumor activity of anti-CTLA-4 antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.ACS nano · 2025Article
- Engineering of pH-dependent antigen binding properties for toxin-targeting IgG1 antibodies using light-chain shuffling.Structure (London, England : 1993) · 2024Article
- Computational design of non-porous pH-responsive antibody nanoparticles.Nature structural & molecular biology · 2024Article
- An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.Nature communications · 2024Article
- A Generic Antibody-Blocking Protein That Enables pH-Switchable Activation of Antibody Activity.ACS chemical biology · 2024Article
- An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.bioRxiv : the preprint server for biology · 2024Article
- Phage display assisted discovery of a pH-dependent anti-α-cobratoxin antibody from a natural variable domain library.Protein science : a publication of the Protein Society · 2023Article
- Comparative Performance of High-Throughput Methods for Protein pJournal of chemical information and modeling · 2023Article
- Enhanced in vivo blood brain barrier transcytosis of macromolecular cargo using an engineered pH-sensitive mouse transferrin receptor binding nanobody.Fluids and barriers of the CNS · 2023Article
- EnhancedbioRxiv : the preprint server for biology · 2023Article
- Combining deep mutational scanning to heatmap of HLA class II binding of immunogenic sequences to preserve functionality and mitigate predicted immunogenicity.Frontiers in immunology · 2023Article
- An Engineered Monovalent Anti-TNF-α Antibody with pH-Sensitive Binding Abrogates Immunogenicity in Mice following a Single Intravenous Dose.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- SpySwitch enables pH- or heat-responsive capture and release for plug-and-display nanoassembly.Nature communications · 2022Article
- Yeast Display Guided Selection of pH-Dependent Binders.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is growing interest in the fast and robust engineering of protein pH-sensitivity that aims to reduce binding at acidic pH, compared to neutral pH. Here, we describe a novel strategy for the incorporation of pH-sensitive antigen binding functions into antibody variable domains using combinatorial histidine scanning libraries and yeast surface display. The strategy allows simultaneous screening for both, high affinity binding at pH 7.4 and pH-sensitivity, and excludes conventional negative selection steps. As proof of concept, we applied this strategy to incorporate pH-dependent antigen binding into the complementary-determining regions of adalimumab. After 3 consecutive rounds of separate heavy and light chain library screening, pH-sensitive variants could be isolated. Heavy and light chain mutations were combined, resulting in 3 full-length antibody variants that revealed sharp, reversible pH-dependent binding profiles. Dissociation rate constants at pH 6.0 increased 230- to 780-fold, while high affinity binding at pH 7.4 in the sub-nanomolar range was retained. Furthermore, binding to huFcRn and thermal stability were not affected by histidine substitutions. Overall, this study emphasizes a generalizable strategy for engineering pH-switch functions potentially applicable to a variety of antibodies and further proteins-based therapeutics.
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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.