title: MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: from bench to bedside.
abstract: The adaptive immune system has been the main focus of immunological strategies in oncology with only more recent approaches targeting innate immunity. Endosomal toll-like receptors (TLR-7, TLR-9) activate innate immune responses by signaling damage-associated molecular patterns (DAMP) from decaying tumor cells. This has led to the development of DNA-based TLR-9 agonists, which induce antitumor activity through innate and subsequent adaptive immune responses. Early clinical trials with CpG-ODN as TLR-9 agonists were associated with unfavorable tolerability and narrow clinical efficacy, leading to failure in pivotal trials. dSLIM, the active ingredient of MGN1703, is a DNA-based, radically different molecular alternative to CpG-ODN, which results in genuine antitumor immunomodulation. Preclinical and clinical studies of MGN1703 have confirmed that this TLR-9 agonist has therapeutic potential in a variety of solid tumors, while long-term treatment with high doses was very well tolerated. A pivotal trial of first-line maintenance treatment with MGN1703 in patients with metastatic colorectal cancer is underway.
authors.affiliation: Foundation Institute Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Arnimallee 22, 14195 Berlin, Germany. Electronic address: bw@zedat.fu-berlin.de.
authors.forename: Burghardt
authors.initials: B
authors.lastname: Wittig
authors.affiliation: Mologen AG, Fabeckstr. 30, 14195 Berlin, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Division of Oncology, Department of Medicine I and Cancer Center, Medical University Vienna, Waehringer Guertel 18-20, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.affiliation: Department of Internal Medicine IV, Haematology & Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schmoll
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004247:DNA / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D007155:Immunologic Factors; C000597235:MGN1703; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D004247:DNA
keywords: Anti-cancer immunomodulation; Colorectal cancer; Innate immune response; MGN1703; Toll-like receptor 9; dSLIM(®)