ArticleJournal for immunotherapy of cancer2020
Fibroblast activation protein-targeted-4-1BB ligand agonist amplifies effector functions of intratumoral T cells in human cancer.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Cibisatamab and FAP-4-1BBL in microsatellite-stable colorectal cancer: a phase 1b trial.Nature medicine · 2026Article
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Targeting Ovarian Neoplasms: Subtypes and Therapeutic Options.Medicina (Kaunas, Lithuania) · 2025Review
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB.Antibodies (Basel, Switzerland) · 2025Article
- Tumor Microenvironment in Melanoma-Characteristic and Clinical Implications.International journal of molecular sciences · 2025Review
- An iterative strategy to design 4-1BB agonist nanobodies de novo with generative AI models.Scientific reports · 2025Article
- 4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models.Journal for immunotherapy of cancer · 2025Article
- Developing innovative strategies of tumor‑infiltrating lymphocyte therapy for tumor treatment.Oncology reports · 2024Review
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- A model-based approach leveraging in vitro data to support dose selection from the outset: A framework for bispecific antibodies in immuno-oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- Delivering co-stimulatory tumor necrosis factor receptor agonism for cancer immunotherapy: past, current and future perspectives.Frontiers in immunology · 2023Review
- Research Progress on Therapeutic Targeting of Cancer-Associated Fibroblasts to Tackle Treatment-Resistant NSCLC.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Charting roadmaps towards novel and safe synergistic immunotherapy combinations.Nature cancer · 2022Review
- DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Article
- Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?Cancers · 2022Review
- Cancer Associated Fibroblasts - An Impediment to Effective Anti-Cancer T Cell Immunity.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe costimulatory receptor 4-1BB (CD137, TNFRSF9) plays an important role in sustaining effective T cell immune responses and is investigated as target for cancer therapy. Systemic 4-1BB directed therapies elicit toxicity or low efficacy, which significantly hampered advancement of 4-1BB-based immunotherapy. Therefore, targeted delivery of 4-1BB agonist to the tumor side is needed for eliciting antitumor efficacy while avoiding systemic toxicity.
methodsWe analyzed the immunostimulatory properties of a fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL) by assessing tumor-infiltrating lymphocytes' (TIL) activity from patients with non-small cell lung cancer and epithelial ovarian cancer.
resultsCombination treatment with FAP-4-1BBL and T cell receptor stimulation by either anti-CD3 or T cell bispecific antibodies significantly enhanced TIL activation and effector functions, including T cell proliferation, secretion of proinflammatory cytokines and cytotoxicity. Notably, costimulation with FAP-4-1BBL led to de novo secretion of interleukin (IL)-13. This was associated with cytokine-mediated tumor cell apoptosis, which was partially dependent on IL-13 alpha 1/2 receptors and STAT6 phosphorylation.
conclusionsOur study provides mechanistic insights into T cell stimulation induced by FAP-4-1BBL in primary human tumors and supports the investigation of FAP-4-1BBL compound in early clinical trials.
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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.