ArticleBlood2016
Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
- Targeting the arginine metabolic brake enhances immunotherapy for leukaemia.International journal of cancer · 2019Trial
- HDAC8 inhibition targets STAT3-MYC axis and synergizes with Venetoclax in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Myeloid derived suppressor cells in neuroblastoma: mechanisms of immune evasion and therapeutic opportunities.Frontiers in immunology · 2026Review
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- PD-L1 autoregulation promotes the proliferation, migration and invasion of glioblastoma cells via GP130/JAK2/STAT3/IRAK2/IL6 signaling pathway.Scientific reports · 2025Article
- Unleashing the TLR9-driven multilineage differentiation of myeloid leukemia cellsMolecular therapy. Nucleic acids · 2025Article
- Advances of signal transducer and activator of transcription 3 inhibitors in acute myeloid leukemia (Review).Oncology letters · 2025Review
- Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition.International journal of molecular sciences · 2024Review
- Bi-functional CpG-STAT3 decoy oligonucleotide triggers multilineage differentiation of acute myeloid leukemia in mice.Molecular therapy. Nucleic acids · 2024Article
- Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review).International journal of oncology · 2024Review
- Oligo-PROTAC strategy for cell-selective and targeted degradation of activated STAT3.Molecular therapy. Nucleic acids · 2024Article
- G3BP1 Interact with JAK2 mRNA to Promote the Malignant Progression of Nasopharyngeal Carcinoma via Activating JAK2/STAT3 Signaling Pathway.International journal of biological sciences · 2024Article
- IL-6/STAT3 signaling in tumor cells restricts the expression of frameshift-derived neoantigens by SMG1 induction.Molecular cancer · 2022Article
- DNA minicircles as novel STAT3 decoy oligodeoxynucleotides endowed with anticancer activity in triple-negative breast cancer.Molecular therapy. Nucleic acids · 2022Article
- Targeting myeloid-derived suppressor cells to enhance natural killer cell-based immunotherapy.Pharmacology & therapeutics · 2022Review
- Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review).Molecular medicine reports · 2022Review
- Tumor-Mediated Neutrophil Polarization and Therapeutic Implications.International journal of molecular sciences · 2022Review
- STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice.Journal for immunotherapy of cancer · 2022Article
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Targeting oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) in acute myeloid leukemia (AML) can reduce blast survival and tumor immune evasion. Decoy oligodeoxynucleotides (dODNs), which comprise STAT3-specific DNA sequences are competitive inhibition of STAT3 transcriptional activity. To deliver STAT3dODN specifically to myeloid cells, we linked STAT3dODN to the Toll-like receptor 9 (TLR9) ligand, cytosine guanine dinucleotide (CpG). The CpG-STAT3dODN conjugates are quickly internalized by human and mouse TLR9(+)immune cells (dendritic cells, B cells) and the majority of patients' derived AML blasts, including leukemia stem/progenitor cells. Following uptake, CpG-STAT3dODNs are released from endosomes, and bind and sequester cytoplasmic STAT3, thereby inhibiting downstream gene expression in target cells. STAT3 inhibition in patients' AML cells limits their immunosuppressive potential by reduced arginase expression, thereby partly restoring T-cell proliferation. Partly chemically modified CpG-STAT3dODNs have >60 hours serum half-life which allows for IV administration to leukemia-bearing mice (50% effective dose ∼ 2.5 mg/kg). Repeated administration of CpG-STAT3dODN resulted in regression of human MV4-11 AML in mice. The antitumor efficacy of this strategy is further enhanced in immunocompetent mice by combining direct leukemia-specific cytotoxicity with immunogenic effects of STAT3 blocking/TLR9 triggering. CpG-STAT3dODN effectively reducedCbfb/MYH11/MplAML burden in various organs and eliminated leukemia stem/progenitor cells, mainly through CD8/CD4 T-cell-mediated immune responses. In contrast, small-molecule Janus kinase 2/STAT3 inhibitor failed to reproduce therapeutic effects of cell-selective CpG-STAT3dODN strategy. These results demonstrate therapeutic potential of CpG-STAT3dODN inhibitors with broad implications for treatment of AML and potentially other hematologic malignancies.
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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.