Development of Toll-like receptor 7 ligand and sugar chain immobilized gold nanoparticles for vaccine adjuvant and immunotherapy

DOI
  • Yamaguchi Toru
    Graduate School of Science and Engineering, Kagoshima University
  • Shinchi Hiroyuki
    Graduate School of Science and Engineering, Kagoshima University
  • Moroishi Toshiro
    Department of Molecular Enzymology, Faculty of Life Sciences, Kumamoto University Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST)
  • Wakao Masahiro
    Graduate School of Science and Engineering, Kagoshima University
  • Hayashi Tomoko
    Moores Cancer Center, University of California, San Diego
  • B. Cottam Howard
    Moores Cancer Center, University of California, San Diego
  • A. Carson Dennis
    Moores Cancer Center, University of California, San Diego
  • Suda Yasuo
    Graduate School of Science and Engineering, Kagoshima University SUDx-Biotech, Corporation

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Other Title
  • 新規アジュバントとしてのTLR7リガンド・糖鎖固定化金ナノ粒子の開発
  • 【優秀演題賞】

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Abstract

<p> Adjuvants enhance immune system during vaccination. Among FDA-approved adjuvants, aluminum salts are most commonly used for vaccines. Although aluminum salts enhance antibody production, they show a limited effect for the cell-mediated immune response. Thus, further development of adjuvants inducing T cell mediated immuno-responses are demanded. Toll-like receptors (TLRs) are immune-related receptors that recognize specific pathogen-associated molecular patterns and play important roles in the activation of innate immunity, which is crucial to shape adaptive immunity. Studies using TLR ligands as novel adjuvants for anti-microbial and anti-cancer immunotherapies have therefore attracted much attention. Among them, a low molecular weight TLR7 ligand, Imiquimod, has been approved for clinical use, but its use is restricted only for local administration due to unwanted adverse effects. Since TLR7 is mainly located in the endosomal compartment of immune cells, efficient transport of the ligand into the cell is important for activating TLR7. Our previous work indicated that the conjugation of a low molecular weight TLR7 ligand with serum albumin and polysaccharides can greatly enhance its potency. In this study, we examined gold nanoparticles (GNPs) as carriers, as GNPs are less toxic and can immobilize multiple molecules including antigens for pathogens and tumors. Furthermore, α-mannose for targeting antigen presenting cells was also examined for the efficient delivery of GNPs. In this paper, we describe preparation of a low molecular weight TLR7 ligand and α-mannose immobilized GNPs and its in vitro and in vivo immunostimulatory activities.</p>

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