ArticlemAbs
Off-target binding of an anti-amyloid beta monoclonal antibody to platelet factor 4 causes acute and chronic toxicity in cynomolgus monkeys.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
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
13 citing papers in PubMed.
- PF4 in rejuvenation therapy: Neuroprotection and cognitive enhancement.Biomolecules & biomedicine · 2025Review
- AI-enhanced profiling of phage-display-identified anti-TIM3 and anti-TIGIT novel antibodies.Frontiers in immunology · 2025Article
- Monoclonal antibodies: From magic bullet to precision weapon.Molecular biomedicine · 2024Review
- Predicting monoclonal antibody binding sequences from a sparse sampling of all possible sequences.Communications biology · 2024Article
- The Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Tools to investigate the cell surface: Proximity as a central concept in glycoRNA biology.Cell chemical biology · 2024Review
- Article
- Physicochemical Stimulus-Responsive Systems Targeted with Antibody Derivatives.Current molecular medicine · 2024Review
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- A New in Silico Antibody Similarity Measure Both Identifies Large Sets of Epitope Binders with Distinct CDRs and Accurately Predicts Off-Target Reactivity.International journal of molecular sciences · 2022Article
- Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1.International journal of molecular sciences · 2022Article
- Review
- Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ABT-736 is a humanized monoclonal antibody generated to target a specific conformation of the amyloid-beta (Aβ) protein oligomer. Development of ABT-736 for Alzheimer's disease was discontinued due to severe adverse effects (AEs) observed in cynomolgus monkey toxicity studies. The acute nature of AEs observed only at the highest doses suggested potential binding of ABT-736 to an abundant plasma protein. Follow-up investigations indicated polyspecificity of ABT-736, including unintended high-affinity binding to monkey and human plasma protein platelet factor 4 (PF-4), known to be involved in heparin-induced thrombocytopenia (HIT) in humans. The chronic AEs observed at the lower doses after repeat administration in monkeys were consistent with HIT pathology. Screening for a backup antibody revealed that ABT-736 possessed additional unintended binding characteristics to other, unknown factors. A subsequently implemented screening funnel focused on nonspecific binding led to the identification of h4D10, a high-affinity Aβ oligomer binding antibody that did not bind PF-4 or other unintended targets and had no AEs
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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.