ArticlePloS one2014
Engineering of bispecific affinity proteins with high affinity for ERBB2 and adaptable binding to albumin.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 58 citations in OpenAlex.
- Phase I Study ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Trial
- Integrating Tumor Targeting and Half-Life Extension into a Dual-Surfaced Single-Domain ADAPT Protein.Molecular pharmaceutics · 2026Article
- Investigating the anticancer properties of starter culture of Tripura: an in-silico study on non-small cell lung cancer.In silico pharmacology · 2025Article
- Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.Theranostics · 2025Article
- Surface-engineered bacteria in drug development.Microbial biotechnology · 2024Review
- Site-directed conjugation of single-stranded DNA to affinity proteins: quantifying the importance of conjugation strategy.Chemical science · 2024Article
- Article
- An easy-to-use high-throughput selection system for the discovery of recombinant protein binders from alternative scaffold libraries.Protein engineering, design & selection : PEDS · 2023Article
- Bacterial Cell Display for Selection of Affibody Molecules.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Experimental HER2-Targeted Therapy Using ADAPT6-ABD-mcDM1 in Mice Bearing SKOV3 Ovarian Cancer Xenografts: Efficacy and Selection of Companion Imaging Counterpart.Pharmaceutics · 2022Article
- Targeting HER2 Expressing Tumors with a Potent Drug Conjugate Based on an Albumin Binding Domain-Derived Affinity Protein.Pharmaceutics · 2021Article
- Small Bispecific Affinity Proteins for Simultaneous Target Binding and Albumin-Associated Half-Life Extension.Molecular pharmaceutics · 2021Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Investigation of a Pharmacological Approach for Reduction of Renal Uptake of Radiolabeled ADAPT Scaffold Protein.Molecules (Basel, Switzerland) · 2020Article
- [EJNMMI research · 2020Article
- Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond.EJNMMI radiopharmacy and chemistry · 2020Review
- HER2-Specific Pseudomonas Exotoxin A PE25 Based Fusions: Influence of Targeting Domain on Target Binding, Toxicity, and In Vivo Biodistribution.Pharmaceutics · 2020Article
- Staphylococcus carnosus: from starter culture to protein engineering platform.Applied microbiology and biotechnology · 2017Review
- Comparative evaluation of tumor targeting using the anti-HER2 ADAPT scaffold protein labeled at the C-terminus with indium-111 or technetium-99m.Scientific reports · 2017Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein.
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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.