ArticlemAbs2018
Hematopoietic cells as site of first-pass catabolism after subcutaneous dosing and contributors to systemic clearance of a monoclonal antibody in mice.
Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.Science advances · 2019Trial
- A Review on Lymphatic Uptake of Large Therapeutic Proteins after Subcutaneous Injection.Pharmaceutical research · 2026Review
- Physiologically Based Pharmacokinetic Modeling of Biologic Case Studies in Monkeys and Humans Reveals the Necessity of an Additional Clearance Term.Pharmaceutics · 2025Article
- A Physiologically Based Pharmacokinetic Model Relates the Subcutaneous Bioavailability of Monoclonal Antibodies to the Saturation of FcRn-Mediated Recycling in Injection-Site-Draining Lymph Nodes.Antibodies (Basel, Switzerland) · 2024Article
- Antibody Drug Clearance: An Underexplored Marker of Outcomes with Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- The therapeutic age of the neonatal Fc receptor.Nature reviews. Immunology · 2023Review
- Predicting Human Bioavailability of Subcutaneously Administered Fusion Proteins and Monoclonal Antibodies Using Human Intravenous Clearance or Antibody Isoelectric Point.The AAPS journal · 2023Article
- Monoclonal Antibody Pharmacokinetics in Cynomolgus Monkeys Following Subcutaneous Administration: Physiologically Based Model Predictions from Physiochemical Properties.The AAPS journal · 2022Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Model-Based Assessment of the Contribution of Monocytes and Macrophages to the Pharmacokinetics of Monoclonal Antibodies.Pharmaceutical research · 2022Article
- A Two-Pore Physiologically Based Pharmacokinetic Model to Predict Subcutaneously Administered Different-Size Antibody/Antibody Fragments.The AAPS journal · 2021Article
- Subcutaneous Site-of-Absorption Study with the Monoclonal Antibody Tocilizumab in Minipigs: Administration Behind Ear Translates Best to Humans.The AAPS journal · 2020Article
- Pharmacokinetic and Pharmacodynamic Properties of Drug Delivery Systems.The Journal of pharmacology and experimental therapeutics · 2019Review
- Pharmacokinetic and Pharmacodynamic Considerations in the Design of Therapeutic Antibodies.Clinical and translational science · 2019Review
- Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.Drug metabolism and pharmacokinetics · 2019Review
- The Neonatal Fc Receptor (FcRn): A Misnomer?Frontiers in immunology · 2019Review
- Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
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Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The neonatal Fc receptor (FcRn) has been demonstrated to contribute to a high bioavailability of monoclonal antibodies (mAbs). In this study, we explored the cellular sites of FcRn-mediated protection after subcutaneous (SC) and intravenous (IV) administration. SC absorption and IV disposition kinetics of a mAb were studied in hFcRn transgenic (Tg) bone marrow chimeric mice in which hFcRn was restricted to radioresistant cells or hematopoietic cells. SC bioavailabilities close to 90% were observed in hFcRn Tg mice and chimeric mice with hFcRn expression in hematopoietic cells, whereas SC bioavailabilities were markedly lower when FcRn was missing in hematopoietic cells. Our study demonstrates: 1) FcRn in radiosensitive hematopoietic cells is required for high SC bioavailability, indicating first-pass catabolism after SC administration by hematopoietic cells; 2) FcRn-mediated transcytosis or recycling by radioresistent cells is not required for high SC bioavailability; and 3) after IV administration hematopoietic and radioresistent cells contribute about equally to clearance of the mAb. A pharmacokinetic model was devised to describe a mixed elimination via radioresistent and hematopoietic cells from vascular and extravascular compartments, respectively. Overall, the study indicates a relevant role of hematopoietic cells for first-pass clearance of mAbs after SC administration and confirms their role in the overall clearance of mAbs.
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What OpenQuestion holds
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.