ArticlePloS one2017
Production of an anti-Aβ antibody fragment in Pichia pastoris and in vitro and in vivo validation of its therapeutic effect.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
16 citing papers in PubMed.
- The landscape of antibody production systems: recombinant expression for research, diagnostics and therapy.Frontiers in bioengineering and biotechnology · 2026Review
- ScFv-h3D6 Prevents Bapineuzumab-Induced Hemorrhagic Events in the APP23 Mouse Model of Alzheimer's Disease.Biomolecules · 2025Article
- A Cost-EffectiveBioengineering (Basel, Switzerland) · 2024Article
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- Structure-Activity Relationship of the Dimeric and Oligomeric Forms of a Cytotoxic Biotherapeutic Based on Diphtheria Toxin.Biomolecules · 2022Article
- Production of Therapeutic Single-Chain Variable Fragments (ScFv) in Pichia pastoris.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The mosaic puzzle of the therapeutic monoclonal antibodies and antibody fragments - A modular transition from full-length immunoglobulins to antibody mimetics.Leukemia research reports · 2022Article
- Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics.Breast cancer (Dove Medical Press) · 2021Review
- Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research.Journal of Alzheimer's disease : JAD · 2021Review
- Application of Antibody Fragments Against Aβ With Emphasis on Combined Application With Nanoparticles in Alzheimer's Disease.Frontiers in pharmacology · 2021Review
- Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer's Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation.Pharmaceutics · 2020Article
- Both Amyloid-β Peptide and Tau Protein Are Affected by an Anti-Amyloid-β Antibody Fragment in Elderly 3xTg-AD Mice.International journal of molecular sciences · 2020Article
- David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments.Antibodies (Basel, Switzerland) · 2019Review
- Pharmacokinetic parameters and mechanism of action of an efficient anti-Aβ single chain antibody fragment.PloS one · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ScFv-h3D6 has been shown as an efficient therapy in the 3xTg-AD mouse model of Alzheimer's Disease. Because one of the major bottlenecks for the therapeutic uses of proteins produced in Escherichia coli is their potential contamination with endotoxins, LPS were extensively removed by a rather low-efficient, expensive, and time-consuming purification step. In addition, disulfide scrambling is favored in the reducing bacterial cytoplasm albeit the use of reductase deficient strains. To overcome these hurdles, as well as to improve the yield, the yeast Pichia pastoris, an endotoxin-free host system for recombinant protein production, has been used to produce scFv-h3D6, both in flask and in a fed-batch bioreactor. Comparison of the thermal stability of the obtained protein with that from E. coli showed no differences. Opposite to the case of the protein obtained from E. coli, no disulfide scrambled conformations or LPS traces were detected in that produced in P. pastoris. Cytotoxicity assays in SH-SY5Y neuroblastoma cell-cultures demonstrated that proteins from both expression systems were similarly efficient in precluding Aβ-induced toxicity. Finally, the 3xTg-AD mouse model was used to test the therapeutic effect of both proteins. Quantification of Aβ levels from cortex and hippocampus protein extracts by ELISA, and Aβ-immunohistochemistry, showed that both proteins reduced Aβ burden. This work demonstrates that scFv-h3D6 obtained from P. pastoris shows the same benefits as those already known for that obtained from E. coli, with multiple advantages in terms of recombinant production and safety.
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