ArticleProceedings of the National Academy of Sciences of the United States of America2020
An engineered 4-1BBL fusion protein with "activity on demand".
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. 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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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, 27 citations in OpenAlex.
- A novel strategy to generate immunocytokines with activity-on-demand using small molecule inhibitors.EMBO molecular medicine · 2024Article
- BRAIDing receptors for cell-specific targeting.eLife · 2024Article
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
- Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.OncoTargets and therapy · 2024Review
- Article
- A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy.Nature biotechnology · 2023Article
- Review
- Targeting Co-Stimulatory Receptors of the TNF Superfamily for Cancer Immunotherapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- Molecular ZIP codes in targeted drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Review
- CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism.Theranostics · 2022Article
- An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineered cytokines are gaining importance in cancer therapy, but these products are often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as a target for therapeutic strategies with agonistic antibodies or using its cognate cytokine ligand, 4-1BBL. Here we describe the engineering of an antibody fusion protein, termed F8-4-1BBL, that does not exhibit cytokine activity in solution but regains biological activity on antigen binding. F8-4-1BBL bound specifically to its cognate antigen, the alternatively spliced EDA domain of fibronectin, and selectively localized to tumors in vivo, as evidenced by quantitative biodistribution experiments. The product promoted a potent antitumor activity in various mouse models of cancer without apparent toxicity at the doses used. F8-4-1BBL represents a prototype for antibody-cytokine fusion proteins, which conditionally display "activity on demand" properties at the site of disease on antigen binding and reduce toxicity to normal tissues.
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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.