ArticleProceedings of the National Academy of Sciences of the United States of America2016
Cell-type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic source.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 74 citations in OpenAlex.
- A robust and scalable immunoadsorbent platform based on the high-affinity M03-IgG antibody for targeted IL-6 Removal in cytokine storm.Frontiers in immunology · 2026Article
- TNFα: TNFR1 signaling inhibits maturation and maintains the pro-inflammatory programming of monocyte-derived macrophages in murine chronic granulomatous disease.Frontiers in immunology · 2024Article
- Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells.Science signaling · 2023Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma.International journal of molecular sciences · 2022Article
- Pharmacogenomics of Anti-TNF Treatment Response Marks a New Era of Tailored Rheumatoid Arthritis Therapy.International journal of molecular sciences · 2022Review
- The renaissance of chemically generated bispecific antibodies.Nature reviews. Chemistry · 2021Review
- Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System.Frontiers in immunology · 2021Article
- Contrasting contributions of TNF from distinct cellular sources in arthritis.Annals of the rheumatic diseases · 2020Article
- Decreased A20 expression on circulating CD56Clinical and experimental immunology · 2019Article
- Post-stroke inflammation-target or tool for therapy?Acta neuropathologica · 2019Review
- Current Approaches and Future Perspectives for Nanobodies in Stroke Diagnostic and Therapy.Antibodies (Basel, Switzerland) · 2019Review
- Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
- A New Venue of TNF Targeting.International journal of molecular sciences · 2018Review
- Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment.Frontiers in immunology · 2018Review
- Principles of Immunotherapy: Implications for Treatment Strategies in Cancer and Infectious Diseases.Frontiers in microbiology · 2018Review
- Non-redundant Functions of IL-6 Produced by Macrophages and Dendritic Cells in Allergic Airway Inflammation.Frontiers in immunology · 2018Article
- Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis.Nature genetics · 2017Article
- Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation.The Journal of experimental medicine · 2017Article
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of TNF contributes to pathogenesis of multiple autoimmune diseases, accounting for a remarkable success of anti-TNF therapy. TNF is produced by a variety of cell types, and it can play either a beneficial or a deleterious role. In particular, in autoimmunity pathogenic TNF may be derived from restricted cellular sources. In this study we evaluated the feasibility of cell-type-restricted TNF inhibition in vivo. To this end, we engineered MYSTI (Myeloid-Specific TNF Inhibitor)--a recombinant bispecific antibody that binds to the F4/80 surface molecule on myeloid cells and to human TNF (hTNF). In macrophage cultures derived from TNF humanized mice MYSTI could capture the secreted hTNF, limiting its bioavailability. Additionally, as evaluated in TNF humanized mice, MYSTI was superior to an otherwise analogous systemic TNF inhibitor in protecting mice from lethal LPS/D-Galactosamine-induced hepatotoxicity. Our results suggest a novel and more specific approach to inhibiting TNF in pathologies primarily driven by macrophage-derived TNF.
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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.