がん免疫療法を促進するDrug Delivery Systemの開発  [in Japanese] Development of a Drug Delivery System for Cancer Immunotherapy  [in Japanese]

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Author(s)

    • 中村 孝司 Nakamura Takashi
    • 北海道大学大学院薬学研究院薬剤分子設計学研究室 Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University

Abstract

 Delivery systems are a powerful technology for enhancing the effect of cancer immunotherapy. We have been in the process of developing lipid-based delivery systems for controlling the physical properties and dynamics of immunofunctional molecules such as antigens and adjuvants. The lipid nanoparticulation of these molecules improves their physical properties, resulting in a good water dispensability, greater stability, and small size. The cell wall skeleton of bacille Calmette-Guerin (BCG-CWS) could be used to replace live BCG as a drug for treating bladder cancer, but problems associated with the physical properties of BCG-CWS have prevented its use. To overcome such problems, we developed a novel packaging method that permits BCG-CWS to be encapsulated into lipid nanoparticles, which induce antitumor responses against bladder cancer. Lipid nanoparticulation also improves the intracellular trafficking and biodistribution of immunofunctional molecules. Cyclic di-GMP (c-di-GMP) is an adjuvant that is recognized by the cytosolic sensor. However, c-di-GMP cannot pass through the cell membrane. We encapsulated c-di-GMP into lipid nanoparticles containing a pH-responsive lipid that was developed in our laboratory and achieved efficient cytosolic delivery and the induction of antitumor immunity. Furthermore, we are attempting to control the functions of immune cells by RNA interference. We have recently succeeded in the efficient delivery of small interfering RNA into mouse dendritic cells (DCs), which led to the enhancement of antitumor activity of DCs. In this review, our recent efforts regarding cancer immunotherapy using lipid-based nanoparticles are reviewed.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 136(11), 1477-1484, 2016

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130005267659
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • ISSN
    0031-6903
  • NDL Article ID
    027725084
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  J-STAGE 
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