ArticleNucleic acid therapeutics2015
Design and Structural Requirements of the Potent and Safe TLR-9 Agonistic Immunomodulator MGN1703.
Article in Nucleic acid therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Trial
- The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.Mucosal immunology · 2018Trial
- Lefitolimod in Combination with Ipilimumab in Patients with Advanced Solid Tumors: A Phase I Trial.Journal of immunotherapy and precision oncology · 2025Article
- Toll-like receptor agonists as cancer vaccine adjuvants.Human vaccines & immunotherapeutics · 2024Review
- TLR9 agonism differentially impacts human NK cell-mediated direct killing and antibody-dependent cell-mediated cytotoxicity.Scientific reports · 2024Article
- Mapping the interplay between NK cells and HIV: therapeutic implications.Journal of leukocyte biology · 2023Review
- Immunotherapy in Small Cell Lung Cancer Treatment: a Promising Headway for Future Perspective.Current treatment options in oncology · 2022Review
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy.Frontiers in cellular and infection microbiology · 2022Article
- CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials.Pharmaceutics · 2021Review
- Front Line Applications and Future Directions of Immunotherapy in Small-Cell Lung Cancer.Cancers · 2021Review
- Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Use of Toll-Like Receptor Agonists in HIV-1 Cure Strategies.Frontiers in immunology · 2020Review
- Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy.Journal of immunology research · 2020Review
- Pattern Recognition Receptor Ligands as an Emerging Therapeutic Agent for Latent HIV-1 Infection.Frontiers in cellular and infection microbiology · 2020Review
- Update on the Biology, Management, and Treatment of Small Cell Lung Cancer (SCLC).Frontiers in oncology · 2020Review
- Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade.Frontiers in immunology · 2020Review
- The role of immunotherapy in small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- EnanDIM - a novel family of L-nucleotide-protected TLR9 agonists for cancer immunotherapy.Journal for immunotherapy of cancer · 2019Article
- Tuning the Tumor Myeloid Microenvironment to Fight Cancer.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Single-stranded oligodeoxynucleotides (ODN), containing nonmethylated cytosine-guanine motifs (CpG ODN), are recognized by the innate immune system as "danger signals." CpG ODN are efficacious immunomodulators but require phosphorothioate (PT) or other backbone modifications for metabolic stability, which cause toxicities in mice and primates. We therefore designed a covalently closed DNA molecule (dSLIM(®)) where two single-stranded loops containing CG motifs are connected through a double-stranded stem in the absence of any nonnatural DNA component. The most promising immunomodulator, MGN1703, comprises two loops of 30 nucleotides containing three CG motifs each, and a connecting stem stem of 28 base pairs. MGN1703 stimulates cytokine secretion [interferon (IFN)-α, IFN-γ, interleukin (IL)-12, IL-6, and IL-2] and activates immune cells by increased expression of CD80, CD40, human leukocyte antigen (HLA)-DR and ICAM-1. Efficacy of immunomodulation strictly depends on the descriptive dumbbell shape and size of the molecule. Variations in stem length and loop size lead to reduced potency of the respective members of the dSLIM(®) class. In a representative mouse model, toxicities from injections of high amounts of a CpG ODN-PT and of MGN1703 were evaluated. The CpG ODN-PT group showed severe organ damage, whereas no such or other pathologies were found in the MGN1703 group. Oncological clinical trials of MGN1703 already confirmed our design.
Indexed as
Identifiers
What OpenQuestion holds
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.