ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Correlations Between Serum IL-6 Levels and Radiation Pneumonitis in Lung Cancer Patients: A Meta-Analysis.Journal of clinical laboratory analysis · 2016Pooled it
- The prognostic and predictive value of peripheral immune-related proteins in patients with lung cancer treated with radiotherapy.Frontiers in oncology · 2025Review
- Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.Molecules (Basel, Switzerland) · 2024Review
- Immune checkpoint inhibitor-related pneumonitis: research advances in prediction and management.Frontiers in immunology · 2024Review
- Article
- Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release.Oncogenesis · 2023Article
- Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling.Annals of translational medicine · 2023Article
- Targeting IL-6 by engineered Lactococcus lactis via surface-displayed affibody.Microbial cell factories · 2022Article
- Identification of lamprey variable lymphocyte receptors that target the brain vasculature.Scientific reports · 2022Article
- Computational epitope binning reveals functional equivalence of sequence-divergent paratopes.Computational and structural biotechnology journal · 2022Article
- MC-LR-induced interaction between M2 macrophage and biliary epithelial cell promotes biliary epithelial cell proliferation and migration through regulating STAT3.Cell biology and toxicology · 2021Article
- Ribonucleotide reductase subunit M2 promotes proliferation and epithelial-mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma.Bioengineered · 2021Article
- Dissecting the impact of target-binding kinetics of protein binders on tumor localization.iScience · 2021Article
- Computationally-guided design and affinity improvement of a protein binder targeting a specific site on HER2.Computational and structural biotechnology journal · 2021Article
- Detection and Neutralization of SARS-CoV-2 Using Non-conventional Variable Lymphocyte Receptor Antibodies of the Evolutionarily Distant Sea Lamprey.Frontiers in immunology · 2021Article
- Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life.ACS omega · 2020Article
- Characterization of Hagfish (Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System.Biomolecules · 2019Article
- Identification of variable lymphocyte receptors that can target therapeutics to pathologically exposed brain extracellular matrix.Science advances · 2019Article
- Synthesis and preclinical investigation ofMolecular biology reports · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune responses for host defense and tumorigenic process. Upregulation of IL-6 is known to constitutively phosphorylate signal transducer and activator of transcription 3 (STAT3), leading to activation of multiple oncogene pathways and inflammatory cascade. Here, we present the development of a high-affinity protein binder, termed repebody, which effectively suppresses non-small cell lung cancer in vivo by blocking the IL-6/STAT3 signaling. We selected a repebody that prevents human IL-6 (hIL-6) from binding to its receptor by a competitive immunoassay, and modulated its binding affinity for hIL-6 up to a picomolar range by a modular approach that mimics the combinatorial assembly of diverse modules to form antigen-specific receptors in nature. The resulting repebody was highly specific for hIL-6, effectively inhibiting the STAT3 phosphorylation in a dose- and binding affinity-response manner in vitro. The repebody was shown to have a remarkable suppression effect on the growth of tumors and STAT3 phosphorylation in xenograft mice with non-small cell lung cancer by blocking the hIL-6/STAT3 signaling. Structural analysis of the repebody and IL-6 complex revealed that the repebody binds the site 2a of hIL-6, overlapping a number of epitope residues at site 2a with gp130, and consequently causes a steric hindrance to the formation of IL-6/IL-6Rα complex. Our results suggest that high-affinity repebody targeting the IL-6/STAT3 pathway can be developed as therapeutics for non-small cell lung cancer.
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