ArticleMolecular genetics and metabolism reports2021
Nonclinical safety evaluation of pabinafusp alfa, an anti-human transferrin receptor antibody and iduronate-2-sulfatase fusion protein, for the treatment of neuronopathic mucopolysaccharidosis type II.
Article in Molecular genetics and metabolism reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Impact of Neonatal Fc Receptor on Transferrin Receptor Antibody Fusion Protein Pharmacokinetics.Pharmaceutics · 2026Article
- Longitudinal pharmacokinetic and safety studies of an antibody-erythropoietin fusion protein for Alzheimer's disease.International journal of pharmaceutics: X · 2025Article
- In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.Fluids and barriers of the CNS · 2025Article
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice.Molecular therapy. Methods & clinical development · 2023Article
- The Effects of a Blood-Brain Barrier Penetrating Erythropoietin in a Mouse Model of Tauopathy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.International journal of molecular sciences · 2022Review
- Drug delivery for neuronopathic lysosomal storage diseases: evolving roles of the blood brain barrier and cerebrospinal fluid.Metabolic brain disease · 2022Review
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- Treatment of Neuronopathic Mucopolysaccharidoses with Blood-Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
- Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice.Molecular therapy. Methods & clinical development · 2022Article
- Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: An Integrated Analysis of Preclinical and Clinical Data.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pabinafusp alfa is a fusion protein comprising a humanized anti-human transferrin receptor (TfR) antibody and human iduronate-2-sulfatase. It was developed as a novel modality to target central nervous system-related symptoms observed in patients with mucopolysaccharidosis type II (MPS II, also known as Hunter syndrome). As the fusion protein contains an entire IgG1 molecule that binds TfR, there may be specific safety concerns, such as unexpected cellular toxicity due to its effector functions or its ability to inhibit iron metabolism, in addition to general safety concerns. Here, we present the comprehensive results of a nonclinical safety assessment of pabinafusp alfa. Pabinafusp alfa did not exhibit effector functions, as assessed by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity studies in TfR-expressing hematopoietic cells. Repeat-dose toxicity studies in cynomolgus monkeys showed that pabinafusp alfa did not induce any significant toxicological changes at doses up to 30 mg/kg/week upon intravenous administration for up to 26 weeks. Interaction of transferrin with TfR was not inhibited by pabinafusp alfa, suggesting that the effect of pabinafusp alfa on the physiological iron transport system is minimal, which was confirmed by toxicity studies in cynomolgus monkeys. These findings suggest that pabinafusp alfa is expected to be safe for long-term use in individuals with MPS II.
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