ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
B Cell Lymphoma Immunotherapy Using TLR9-Targeted Oligonucleotide STAT3 Inhibitors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Myeloid cell-targeted lipid nanoparticles for B cell lymphoma immunotherapy.Molecular therapy. Nucleic acids · 2025Article
- Cell-selective telomere damage by thiopurine-based oligonucleotide for diffuse large B cell lymphoma immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Decoy-PROTAC for specific degradation of "Undruggable" STAT3 transcription factor.Cell death & disease · 2025Article
- Local CpG-Molecular therapy. Nucleic acids · 2024Article
- Bi-functional CpG-STAT3 decoy oligonucleotide triggers multilineage differentiation of acute myeloid leukemia in mice.Molecular therapy. Nucleic acids · 2024Article
- Oligo-PROTAC strategy for cell-selective and targeted degradation of activated STAT3.Molecular therapy. Nucleic acids · 2024Article
- Specific Targeting of STAT3 in B Cells Suppresses Progression of B Cell Lymphoma.International journal of molecular sciences · 2023Article
- Review
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.BioImpacts : BI · 2022Review
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
- Coordinated regulation of immune contexture: crosstalk between STAT3 and immune cells during breast cancer progression.Cell communication and signaling : CCS · 2021Review
- Targeted In Vivo Delivery of NF-κB Decoy Inhibitor Augments Sensitivity of B Cell Lymphoma to Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors.Cancer immunology research · 2020Article
- Pharmacological Inhibition of Oncogenic STAT3 and STAT5 Signaling in Hematopoietic Cancers.Cancers · 2020Review
- Targeting STAT3 in Cancer with Nucleotide Therapeutics.Cancers · 2019Review
- The Role of Toll-Like Receptors in Oncotherapy.Oncology research · 2019Review
- Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions.British journal of haematology · 2019Review
- Aptamer-iRNAs as Therapeutics for Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Review
- Decoy-Based, Targeted Inhibition of STAT3: A New Step forward for B Cell Lymphoma Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells. We further demonstrated that injections (i.v.) of CpG-STAT3dODN inhibited growth of human OCI-Ly3 lymphoma in immunodeficient mice. Moreover, systemic CpG-STAT3dODN administration induced complete regression of the syngeneic A20 lymphoma, resulting in long-term survival of immunocompetent mice. Both TLR9 stimulation and concurrent STAT3 inhibition were critical for immune-mediated therapeutic effects, since neither CpG7909 alone nor CpG7909 co-injected with unconjugated STAT3dODN extended mouse survival. The CpG-STAT3dODN induced expression of genes critical to antigen-processing/presentation and Th1 cell activation while suppressing survival signaling. These effects resulted in the generation of lymphoma cell-specific CD8/CD4-dependent T cell immunity protecting mice from tumor rechallenge. Our results suggest that CpG-STAT3dODN as a systemic/local monotherapy or in combination with PD1 blockade can provide an opportunity for treating patients with B cell NHL.
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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.