The clinical potential of Affibody-based inhibitors of C5 for therapeutic complement disruption

Berglund, Magnus; Strömberg, Patrik

doi:10.1586/14789450.2016.1148604

Cited by 9 publications

(3 citation statements)

References 18 publications

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“…Another protein-based C5 inhibitor in preclinical stages is the SOBI005 (Sobi). In contrast to its predecessor (SOBI002), which was associated with transient adverse events that led to termination of a clinical trial 91,92 , SOBI005 is fused to the Fc fragment of IgG1 rather than to an albumin-binding entity as a strategy to increase its half-life.…”

Section: Complement-targeting Therapeuticsmentioning

confidence: 99%

The renaissance of complement therapeutics

et al. 2017

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The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.

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Section: Complement-targeting Therapeuticsmentioning

confidence: 99%

The renaissance of complement therapeutics

et al. 2017

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“…An ABD-fused anti-C5 Affibody molecule that could inhibit C5-dependent hemolysis in vitro and potently block C5 in vivo in a Zymosan-induced peritonitis mouse model was recently tested in healthy volunteers (NCT02083666). 74 …”

Section: Towards Therapeutic Application Of Affibody Moleculesmentioning

confidence: 99%

Affibody molecules as engineered protein drugs

Frejd

Kim²

2017

Exp Mol Med

174

147

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Affibody molecules can be used as tools for molecular recognition in diagnostic and therapeutic applications. There are several preclinical studies reported on diagnostic and therapeutic use of this molecular class of alternative scaffolds, and early clinical evidence is now beginning to accumulate that suggests the Affibody molecules to be efficacious and safe in man. The small size and ease of engineering make Affibody molecules suitable for use in multispecific constructs where AffiMabs is one such that offers the option to potentiate antibodies for use in complex disease.

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“…Unlike downstream manufacturing of antibodies, which relies on Protein A-based capture technology, the purification of affibodies does not yet benefit from an established platform technology. Thus, despite their therapeutic potential [28] and having received Food and Drug Administration (FDA) approval for clinical treatment [29], affibodies are available on the market in limited amounts and high price. The development of an affinity-based capture technology targeting the constant regions of affibodies in α-helix 3 and α-helix 1 holds great promise toward streamlining the manufacturing of affibodies and reducing their cost.…”

Section: Introductionmentioning

confidence: 99%

Affibody-Binding Ligands

Barozzi

Lavoie

Day

et al. 2020

IJMS

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While antibodies remain established therapeutic and diagnostic tools, other protein scaffolds are emerging as effective and safer alternatives. Affibodies in particular are a new class of small proteins marketed as bio-analytic reagents. They feature tailorable binding affinity, low immunogenicity, high tissue permeation, and high expression titer in bacterial hosts. This work presents the development of affibody-binding peptides to be utilized as ligands for their purification from bacterial lysates. Affibody-binding candidates were identified by screening a peptide library simultaneously against two model affibodies (anti-immunoglobulin G (IgG) and anti-albumin) with the aim of selecting peptides targeting the conserved domain of affibodies. An ensemble of homologous sequences identified from screening was synthesized on Toyopearl® resin and evaluated via binding studies to select sequences that afford high product binding and recovery. The affibody–peptide interaction was also evaluated by in silico docking, which corroborated the targeting of the conserved domain. Ligand IGKQRI was validated through purification of an anti-ErbB2 affibody from an Escherichia coli lysate. The values of binding capacity (~5 mg affibody per mL of resin), affinity (KD ~1 μM), recovery and purity (64–71% and 86–91%), and resin lifetime (100 cycles) demonstrate that IGKQRI can be employed as ligand in affibody purification processes.

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The clinical potential of Affibody-based inhibitors of C5 for therapeutic complement disruption

Cited by 9 publications

References 18 publications

The renaissance of complement therapeutics

The renaissance of complement therapeutics

Affibody molecules as engineered protein drugs

Affibody-Binding Ligands

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