Development of exosome-capturing antibody-conjugated nucleic acid medicines against multiple myeloma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08826
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Ashihara Eishi 京都薬科大学, 薬学部, 教授 (70275197)
• Co-Investigator(Kenkyū-buntansha): 戸田 侑紀 京都薬科大学, 薬学部, 助教 (40779724) ; 河嶋 秀和 京都薬科大学, 薬学部, 准教授 (70359438)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 多発性骨髄腫 / エクソゾーム / CD63 / 核酸医薬 / 抗体薬物複合体 / 造血器腫瘍 / 急性リンパ芽球性白血病 / ドラッグデリバリーシステム

Outline of Final Research Achievements

Although nucleic acid medicines are expected to function as new therapeutic agents, their targeted delivery into cancer cells, particularly hematologic cancer cells, via systemic administration, is limited. Based on our previous finding that tumor cell-derived exosomes are preferentially incorporated into their parental cancer cells, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNA) with an arginine linker to deliver siRNAs into multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated complexes were incorporated into MM cells. Moreover, these exosome-capturing mAb-conjugated siRNAs successfully decreased the mRNA transcript levels of targeted mRNAs in the MM cells. This technology could lead to a breakthrough in drug delivery systems for hematologic cancer therapy.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、MM細胞から放出されたエクソゾームがMM細胞に取り込まれることを利用し、“Exo捕捉型核酸医薬品”が多発性骨髄腫治療に有効である可能性が示された。この新技術は、有効なDDSが存在しない造血器腫瘍細胞や血液細胞への核酸医薬品送達へと応用できる。さらには固形腫瘍患者さんへの治療にも展開でき、また核酸医薬のみならず化学療法薬や分子標的治療薬の送達にも応用できる。本研究の技術は多くのがん患者さんに福音をもたらすことができる。