| 研究課題/領域番号 |
22K12833
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| 研究機関 | 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター) |
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研究代表者 |
劉 学瑩 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (30777470)
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| 研究分担者 |
喜納 宏昭 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 主幹研究員 (70283067)
Quader Sabina 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 主任研究員 (90749699)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| キーワード | Nanomedicine / chemo-immunotherapy / medulloblastoma |
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| 研究実績の概要 |
For this project, we proposed to generate and validate a syngeneic mouse model of medulloblastoma and understand the potential of a tumor pH-sensitive NM loaded with ICD-inducing drug modulating tumor immune environment against MB. Towards these aims, we managed to achieve the following research outcomes-
Generate and validate a syngeneic mouse model of medulloblastoma (MB) - Dr. Robert Wechsler-Reya's laboratory at Sanford Burnham Prebys Medical Discovery Institute, CA, United States, established several MB syngeneic models. One of the collaborating investigators (Co-I), Dr. Sabina Quader, could successfully initiate a research collaboration with Dr. Wechsler-Reya. Through this collaboration we created a syngeneic mouse model of MB in our laboratory. We consider this a significant advancement in our MB-related research, as developing a syngeneic mouse model is critical for immune-related studies against MB.
Collect preliminary research results using tumor pH-sensitive NM loaded with ICD-inducing drug against MB syngeneic model- We have successfully completed our preliminary research studies using tumor pH-sensitive NM loaded with ICD-inducing drug against MB syngeneic model. Based on the results of these studies, we are now moving on to the next phase of studies, where we are considering examining the potential of using immune checkpoint inhibitors.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We could successfully generate a syngeneic mouse model of medulloblastoma, which is a significant part of the proposed research.
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| 今後の研究の推進方策 |
Defining the Tumor Immune Microenvironment status of the developed syngeneic MB tumor-and designing the most appropriate ICI therapy strategy-
A wide variety of immune cells play a crucial part in the brain tumor’s immune microenvironment (TIME) throughout the complex and dynamic process of tumorigenesis, where they create complex contacts with tumor cells and one another to form a convoluted network. Dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, tumor-associated macrophages, CD8+ T cells, and neutrophils are a few examples of immune cells that each play a different role in the biology of brain tumors. Therefore, assessing the established syngeneic mouse model's accurate immune landscape would be crucial. This would then be used to analyze ICD factors such as tumor-infiltrating T cells' presence and activation status, expression of the immunological checkpoint PD1/PDL1, or the assessment of the tumor mutational burden. A suitable ICI therapy will be chosen on the basis of this evaluation.
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| 次年度使用額が生じた理由 |
One of our planned expense for the initial year of research was to buy a SmoA1 mouse model ND2:SmoA1 which would incur a significant amount of research expenses. Due to a collaboration opportunity, we could establish a syngeneic medulloblastoma mouse model without having to buy ND2:SmoA1 mouse. Therefore, our actual research expense was lower than our planned research expenses.
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