Development of exosome-capturing antibody-conjugated nucleic acid medicines against multiple myeloma
Project/Area Number |
19K08826
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Kyoto Pharmaceutical University |
Principal Investigator |
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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)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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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 / エクソソーム |
Outline of Research at the Start |
本申請研究は、研究代表者が発見したエクソソームの細胞指向性送達理論に基づく、エクソソームの表面抗原に対する抗体とsiRNAを結合させた新規の機能分子開発研究で、この“エクソソーム捕捉型核酸医薬品”を用いて、多発性骨髄腫に対する新たな治療法を開発する。今回開発する新規の抗体結合型siRNAが多発性骨髄腫治療に有効であることが示されれば、この技術は広く各種造血器悪性腫瘍患者さん、さらには固形腫瘍患者さんへの治療にも展開できる。また分子標的小分子化合物のconjugate作製にも展開でき、本研究の技術は多くのがん患者さんに福音をもたらす可能性を有する。
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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.
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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。
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Factors Associated with Dose Modification of Lenalidomide Plus Dexamethasone Therapy in Multiple Myeloma2020
Author(s)
Yoko Kado, Masayuki Tsujimoto, Shin-ichi Fuchida, Akira Okano, Mayumi Hatsuse, Satoshi Murakami, Hikofumi Sugii, Kumi Ueda, Yuki Toda, Tetsuya Minegaki, Kohshi Nishiguchi, Yuichi Muraki, Chihiro Shimazaki, Eishi Ashihara.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 43
Issue: 8
Pages: 1253-1258
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2020-08-01
Related Report
Peer Reviewed
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[Journal Article] Peripheral blood-derived microglia-like cells decrease amyloid-β burden and ameliorate cognitive impairment in a mouse model of Alzheimer’s disease.2020
Author(s)
Kuroda E., Takata K., Nishimura K., Oka H., Sueyoshi M., Aitani M., Kouda A., Satake S., Shima C., Toda Y., Nakata S., Kitamura Y., and Ashihara E.
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Journal Title
J. Alzheimers Dis.
Volume: 73 (1)
Issue: 1
Pages: 413-429
DOI
Related Report
Peer Reviewed
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[Presentation] ovel BET/CBP/p300 multi-bromodomain inhibitors as a strategy for MLL-rearranged ALL.2020
Author(s)
Natsuki Imayoshi, Makoto Yoshioka, Kuniaki Tanaka, Shyh-Ming Yang, Koshi Akahane, Yuki Toda, Shigekuni Hosogi, Takeshi Inukai, Seiji Okada, David J. Maloney, Itaru Kato, Eishi Ashihara.
Organizer
第82回日本血液学会学術集会
Related Report
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[Presentation] Application of BET/CBP/p300 multi-bromodomain inhibitors as a novel therapeutic strategy for MLL-rearranged acute lymphoblastic leukemia.2020
Author(s)
Natsuki Imayoshi, Makoto Yoshioka, Shyh-Ming Yang, Koshi Akahane, Yuki Toda, Shigekuni Hosogi, Takeshi Inukai, Seiji Okada, David J. Maloney, Jeffrey W. Strovel, Eishi Ashihara.
Organizer
American Association for Cancer Research (AACR) Annual Meeting 2020
Related Report
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[Presentation] Anti-tumor effects of a novel Wnt/β-catenin pathway inhibitor against acute myelogenous leukemia.2020
Author(s)
Ryosuke Wakabayashi, Yasunao Hattori, Yusuke Sano, Yuki Sugiyama, Natsuki Imayoshi, Makou Tomogane, Keigo Amari, Yuki Toda, Kazuya Kobayashi, Shigekuni Hosogi, Kenichi Akaji, Eishi Ashihara.
Organizer
The 3rd International Cancer Research Symposium
Related Report
Int'l Joint Research
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