ArticleScientific reports2018
Assessing the Feasibility of Neutralizing Osteopontin with Various Therapeutic Antibody Modalities.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Targeting SPP1 requires moving beyond ligand blockade.Cellular & molecular immunology · 2026Article
- Osteopontin mediates acquired resistance to hypoxia-inducing antiangiogenics and promotes anti-PD-L1 refractoriness in breast cancer models.The Journal of clinical investigation · 2026Article
- POSTN(+) fibroblasts and SPP1(+) macrophages in scar formation: A review of mechanisms and therapeutic targets (Review).Molecular medicine reports · 2026Review
- Research progress on the correlation between OPN and immune escape of gastric cancer.Clinical and experimental medicine · 2026Review
- Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches.Cancer cell · 2025Article
- Article
- Proteins and pathways involved in inflammation are longitudinally associated with total body bone mineral density among primarily Hispanic overweight/obese adolescents and young adults.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Changes in Nucleus Pulposus Cell Atlas and the Role of SPP1 During Intervertebral Disc Degeneration: Single-Cell Sequencing Analysis.Mediators of inflammation · 2025Article
- Relationships between Osteopontin, Osteoprotegerin, and Other Extracellular Matrix Proteins in Calcifying Arteries.Biomedicines · 2024Article
- Exposure to per- and polyfluoroalkyl substances and high-throughput proteomics in Hispanic youth.Environment international · 2024Article
- Osteogenic stimulation of osteoprogenitors by putamen ovi peptides and hyaluronic acid.Head & face medicine · 2023Article
- Review
- Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model.Leukemia · 2023Article
- Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology.Biomolecules · 2023Review
- A targeted isotope dilution mass spectrometry assay for osteopontin quantification in plasma of metastatic breast cancer patients.PloS one · 2023Article
- Systemic mesalazine treatment prevents spontaneous skin fibrosis in PLK2-deficient mice.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Osteopontin Blockade Immunotherapy Increases Cytotoxic T Lymphocyte Lytic Activity and Suppresses Colon Tumor Progression.Cancers · 2021Article
- A Mechanistic Site-Of-Action Model: A Tool for Informing Right Target, Right Compound, And Right Dose for Therapeutic Antagonistic Antibody Programs.Frontiers in bioinformatics · 2021Article
- Review
- A Physiologically-Based Pharmacokinetic Model for the Prediction of "Half-Life Extension" and "Catch and Release" Monoclonal Antibody Pharmacokinetics.CPT: pharmacometrics & systems pharmacology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteopontin is a secreted glycophosphoprotein that is highly implicated in many physiological and pathological processes such as biomineralization, cell-mediated immunity, inflammation, fibrosis, cell survival, tumorigenesis and metastasis. Antibodies against osteopontin have been actively pursued as potential therapeutics for various diseases by pharmaceutical companies and academic laboratories. Many studies have demonstrated the efficacy of osteopontin inhibition in a variety of preclinical models of diseases such as rheumatoid arthritis, cancer, nonalcoholic steatohepatitis, but clinical utility has not yet been demonstrated. To evaluate the feasibility of osteopontin neutralization with antibodies in a clinical setting, we measured its physiological turnover rate in humans, a sensitive parameter required for mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Results from a stable isotope-labelled amino acid pulse-chase study in healthy human subjects followed by mass spectrometry showed that osteopontin undergoes very rapid turnover. PK/PD modeling and simulation of different theoretical scenarios reveal that achieving sufficient target coverage using antibodies can be very challenging mostly due to osteopontin's fast turnover, as well as its relatively high plasma concentrations in human. Therapeutic antibodies against osteopontin would need to be engineered to have much extended PK than conventional antibodies, and be administered at high doses and with short dosing intervals.
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