Activation of dendritic cells by the novel Toll-like receptor 3 agonist RGC100.
Toll-like receptor (TLR) 3 agonists emerged as attractive candidates for vaccination strategies against tumors and pathogens. An important mechanism of action of such agonists is based on the activation of TLR3-expressing dendritic cells (DCs), which display a unique capacity to induce and stimulate T-cell responses. In this context, it has been demonstrated that targeting of TLR3 by double-stranded RNA such as poly(I:C) results in potent activation of DCs. Major disadvantages of poly(I:C) comprise its undefined chemical structure and very poor homogeneity, with subsequent unpredictable pharmacokinetics and high toxicity. In the present study, we evaluated the physicochemical properties and biological activity of the novel TLR3 agonist RGC100. RGC100 has a defined chemical structure, with a defined length (100 bp) and molecular weight (64.9 KDa) and a good solubility. RGC100 is stable in serum and activates myeloid DCs through TLR3 targeting, as evidenced by gene silencing experiments. Activation of mouse and human myeloid CD1c(+) DCs by RGC100 leads to secretion of several proinflammatory cytokines. In addition, RGC100 improves the ability of CD1c(+) DCs to stimulate T-cell proliferation. Due to its physicochemical properties and its immunostimulatory properties, RGC100 may represent a promising adjuvant for prophylactic and therapeutic vaccination strategies.
Riboxx GmbH, Meissner Straße 191, 01445 Radebeul, Germany.
Kai
K
Naumann
Institute of Immunology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden, Germany.
Rebekka
R
Wehner
Institute of Immunology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden, Germany.
Anett
A
Schwarze
Riboxx GmbH, Meissner Straße 191, 01445 Radebeul, Germany.
Christiane
C
Petzold
Institute of Immunology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden, Germany.
Marc
M
Schmitz
Riboxx GmbH, Meissner Straße 191, 01445 Radebeul, Germany ; Institute of Virology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden, Germany.
Jacques
J
Rohayem
D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D004355:Drug Stability; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D011070:Poly I-C / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
D008024:Ligands; C000590226:RGC100; D051196:Toll-Like Receptor 3; D012313:RNA; D011070:Poly I-C