Affinity proteins and their generation

Ståhl, Stefan; Kronqvist, Nina; Jonsson, Andreas; Löfblom, John

doi:10.1002/jctb.3929

Cited by 16 publications

(5 citation statements)

References 175 publications

(307 reference statements)

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“…A variety of targeting ligands, principally antibodies, , transferrin, , folate, polypeptides, , DNA aptamers, and carbohydrates, have been employed to endow particles with targeting ability. Another class of targeting ligands that are of increasing interest is nonimmunoglobulin-based affinity proteins. , A prominent example in this class, the affibody (Afb), is a small (∼6 kDa), bacterially derived, and recombinantly engineered protein affinity ligand . Afbs have been engineered to bind to a wide range of specific targets, e.g., the human epidermal growth factor receptor 2 (HER2), to which it has picomolar affinity .…”

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confidence: 99%

Targeting Ability of Affibody-Functionalized Particles Is Enhanced by Albumin but Inhibited by Serum Coronas

et al. 2015

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Protein coronas formed on engineered particles can alter their targeting ability as they enter biological environments. Here, we engineer polymer coated silica particles and investigate the influence of protein coronas derived from various sources. The particles were functionalized with a small antibody-mimetic ligand (affibody), and their targeting ability to cancer cells in the presence of protein coronas was determined. Protein coronas derived from human serum showed a dramatic inhibition of specific particle-cell association (from ~70 to ~7%), whereas the most abundant protein in human serum-human serum albumin-enhanced the specific association of functionalized particles to SK-OV-3 human ovary cancer cells (to ~90%). This study shows how protein coronas can both facilitate and impede targeting and provides key insights into the importance of challenging engineered particles with multi-component biologically relevant environments. 'click' chemistry) at the other end (Mal-PEG-Az). The ASSOCIATED CONTENT Supporting Information. Experimental methods, materials, and supplementary figures. This material is available free of charge via the Internet at http://pubs.acs.org.

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confidence: 99%

Targeting Ability of Affibody-Functionalized Particles Is Enhanced by Albumin but Inhibited by Serum Coronas

et al. 2015

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“…Peptide aptamers are produced by protein engineering from high-complexity combinatorial libraries with appropriate isolation/selection methods (82,80,81). Thus, a need to have knowledge of the protein structure and the mechanism behind binding is not necessary.…”

Section: Perspectives For Peptide Lectin Aptamersmentioning

confidence: 99%

Perspectives in Glycomics and Lectin Engineering

Tkac

Bertók

Nahálka

et al. 2014

Methods in Molecular Biology

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“…In addition to monoclonal antibodies and antibody derivatives, several non-immunoglobulin scaffold affinity proteins have been developed [7]. One such scaffold is the affibody molecule, a small (approximately 7 kDa) three-helical bundle consisting of 58 amino acids based on the staphylococcal protein A derived Z-domain [8].…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model

et al. 2020

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Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis. We have previously evaluated the biodistribution profiles of five mono- and bivalent anti-HER3 affibody molecules (designated as 3) fused to an albumin-binding domain (designated as A), 3A, 33A, 3A3, A33, and A3, that inhibit ligand-dependent phosphorylation. In the present study, we examined the therapeutic efficacy of the three most promising variants, 3A, 33A, and 3A3, in a direct comparison with the HER3-targeting monoclonal antibody seribantumab (MM-121) in a preclinical BxPC-3 pancreatic cancer model. Xenografted mice were treated with either an affibody construct or MM-121 and the tumor growth was compared to a vehicle group. Receptor occupancy was estimated by positron emission tomography/computed tomography (PET/CT) imaging using a HER3-targeting affibody imaging agent [68Ga]Ga-(HE)3-Z08698-NODAGA. The affibody molecules could inhibit ligand-dependent phosphorylation and cell proliferation in vitro and demonstrated tumor growth inhibition in vivo comparable to that of MM-121. PET/CT imaging showed full receptor occupancy for all tested drug candidates. Treatment with 3A and 3A3 affibody constructs was more efficient than with 33A and similar to the anti-HER3 antibody seribantumab, showing that the molecular design of affibody-based therapeutics targeting HER3 in terms of the relative position of functional domains and valency has an impact on therapeutic effect.

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Affinity proteins and their generation

Cited by 16 publications

References 175 publications

Targeting Ability of Affibody-Functionalized Particles Is Enhanced by Albumin but Inhibited by Serum Coronas

Targeting Ability of Affibody-Functionalized Particles Is Enhanced by Albumin but Inhibited by Serum Coronas

Perspectives in Glycomics and Lectin Engineering

Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model

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