ArticleOncoimmunology
M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 148 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
148 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a meta-analysis based on mixed-effect models.Frontiers in medicine · 2023Pooled it
- Durable responses to triplet immunotherapy targeting TGF-β, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2020Trial
- Trial
- Development of a novel immune infiltration-based gene signature to predict prognosis and immunotherapy response of a novel anti-PD-L1/TGF-β bifunctional fusion protein in recurrent cervical cancer.Human vaccines & immunotherapeutics · 2026Article
- Endolysosomal routing combined with immune stimulation enhances anti-tumor efficacy of an HPV16 mRNA therapeutic vaccine.Materials today. Bio · 2026Article
- Cold and hot tumors: immunological determinants, cancer-immunity cycle dysregulation, and nanotechnology-driven therapeutic approaches.Molecular biomedicine · 2026Review
- Molecular mechanisms for sustaining cancer stem cells characteristics and targeted therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
- Increased Peripheral T Stem Cell-like Memory Features in Patients with Advanced Solid Tumors Treated with Tumor-Targeting IL-12 Immunocytokine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Phenotypic and targeted drug discovery in immune therapeutics: challenges, opportunities, and future directions.RSC advances · 2025Review
- Advancement insights in cancer vaccines: mechanisms, types, and clinical applications.Molecular biology reports · 2025Review
- Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.Nature communications · 2025Article
- Potential and development of cellular vesicle vaccines in cancer immunotherapy.Discover oncology · 2025Review
- Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis.Frontiers in oncology · 2025Review
- Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.International journal of biological sciences · 2025Review
- A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance.Cancer biology & therapy · 2024Review
- Tumor Biomechanics-Inspired Future Medicine.Cancers · 2024Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection.2019
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1). We demonstrate that M7824 reduces plasma TGFβ1, binds to PD-L1 in the tumor, and decreases TGFβ-induced signaling in the tumor microenvironment in mice. In murine breast and colon carcinoma models, M7824 decreased tumor burden and increased overall survival as compared to targeting TGFβ alone. M7824 treatment promoted CD8+ T cell and NK cell activation, and both of these immune populations were required for optimal M7824-mediated tumor control. M7824 was superior to TGFβ- or αPD-L1-targeted therapies when in combination with a therapeutic cancer vaccine. These findings demonstrate the value of using M7824 to simultaneously target TGFβ and PD-L1/PD-1 immunosuppressive pathways to promote anti-tumor responses and efficacy. The studies also support the potential clinical use of M7824 as a monotherapy or in combination with other immunotherapies, such as therapeutic cancer vaccines, including for patients who have progressed on αPD-L1/αPD-1 checkpoint blockade therapies.
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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.