ArticleJournal for immunotherapy of cancer2021
Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 54 citations in OpenAlex.
- Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma.Signal transduction and targeted therapy · 2025Trial
- FTL008.16, a 5T4-Conditional 4-1BB bispecific antibody, potently enhances antitumor immunity via tumor-directed t-cell activation.Oncoimmunology · 2026Article
- Review
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Article
- Clinical Development of Bispecific Antibodies: Review, Advances, and Challenges in Hematological Malignancies.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Systemic therapy for gastroenteropancreatic neuroendocrine neoplasms: current landscape and future directions.Therapeutic advances in medical oncology · 2026Review
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.British journal of cancer · 2025Review
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- Preclinical Evaluation of DB-1419, a Novel Bifunctional and Bispecific Anti-B7-H3 × PD-L1 Antibody-Drug Conjugate.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- An iterative strategy to design 4-1BB agonist nanobodies de novo with generative AI models.Scientific reports · 2025Article
- Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.Journal for immunotherapy of cancer · 2025Article
- Fc-competent TIGITx4-1BB bispecific antibody exerts potent long-lasting antitumor activity by potentiating CD8Journal for immunotherapy of cancer · 2025Article
- A novel HVEM-Fc recombinant protein for lung cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Article
- A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.Journal of translational medicine · 2025Article
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- The 41BB-agonist potentiates the therapeutic efficacy of a combined irreversible electroporation ablation treatment of lung cancer by promoting unexpected CD8Frontiers in immunology · 2025Article
- Incorporating mRNA therapeutics into biological treatments of hematologic malignancies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStimulation of 4-1BB with agonistic antibodies is a promising strategy for improving the therapeutic efficacy of immune checkpoint inhibitors (ICIs) or for overcoming resistance to ICIs. However, dose-dependent hepatotoxicity was observed in clinical trials with monoclonal anti-4-1BB agonistic antibodies due to the activation of 4-1BB signaling in liver resident Kupffer cells.
methodsTo avoid this on-target liver toxicity, we developed a novel bispecific antibody (4-1BB×PD-L1 bispecific antibody, termed "ABL503") uniquely designed to activate 4-1BB signaling only in the context of PD-L1, while also blocking PD-1/PD-L1 signaling.
resultsFunctional evaluation using effector cells expressing both 4-1BB and PD-1 revealed superior biological activity of ABL503 compared with the combination of each monoclonal antibody. ABL503 also augmented T-cell activation in in vitro assays and further enhanced the anti-PD-L1-mediated reinvigoration of tumor-infiltrating CD8
conclusionThe novel anti-4-1BB×PD-L1 bispecific antibody may exert a strong anti-tumor therapeutic efficacy with a low risk of liver toxicity through the restriction of 4-1BB stimulation in tumors.
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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.