Creation of a lymphatic drug delivery system: controlling distant metastasis and immune-related adverse events
Project/Area Number |
22K18203
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 90130:Medical systems-related
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Research Institution | Tohoku University |
Principal Investigator |
|
Project Period (FY) |
2022-04-01 – 2025-03-31
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Project Status |
Granted (Fiscal Year 2022)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | リンパ節 / 治療 / 転移 / DDS / 薬物送達 / 肺転移 / 免疫 / 有害事象 |
Outline of Research at the Start |
本研究ではLDDSを用いてICIを所属リンパ節に直接投与し,リンパ節およびリンパ節を介した血行性転移に対する超早期治療法の開発, およびirAE発症機序の解明を目的にする. 以下課題に取り組む. (1)LDDSを用いたICIの所属リンパ節投与による治療適用範囲をリンパ節転移から遠隔転移の制御・予防まで拡大する. (2) LDDSの治療効果を高めるためにICIと抗がん剤との重畳効果を検討する. (3) 治療効果を判定するために新たな薬力学的評価因子であるanenestic バイオマーカーを同定する.
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Outline of Annual Research Achievements |
This fiscal year, we aim to investigate immune check inhibitor (ICI) against lymph node metastasis and onset development of irAE during treatment, we worked on the following issues. (1) Evaluation of treatment outcome of immune check point inhibitor (ICI) for local control and prevention of lung metastasis via lymphatic drug delivery system (LDDS). MXH10/Mo/lpr mice were inoculated with tumor cells into the subiliac lymph node (SiLN), and CTLA4 was injected into tumor-inoculated SiLN on day 4 and 8 after inoculation. 10 mg/kg CTLA4 was able to inhibit tumor growth in the SiLN for one-side inoculation group, whereas SiLN and lung in both-side inoculation group with reduced irAEs such as sialadenitis and pneumonia. (2) To improve treatment outcome with reduced irAE, we are using anticancer drug with ICI through the LDDS. MXH10/Mo/lpr mice were inoculated with tumor cells into the SiLN, and chemoimmunotherapy is performed with combination of Doxorubicin and CTLA4 into tumor-inoculated SiLN on different sequences and days to optimize perfect combination.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
As per the application form for issuance.
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Strategy for Future Research Activity |
(1) Evaluation of treatment outcome of immune check point inhibitor (ICI) for local control and prevention of lung metastasis via lymphatic drug delivery system (LDDS). We will continue the experiment for activation of lung metastasis after lymphadenopathy. (2) To improve treatment outcome with reduced irAE, we are using anticancer drug with ICI through the LDDS. We will conduct an experiment on chemoimmunotherapy with combination of Doxorubicin and CTLA4 via LDDS.
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Report
(1 results)
Research Products
(10 results)