2020 Fiscal Year Annual Research Report
SynNotch EV cells-flexible ”CAR T”-cells
| Project/Area Number |
19K16849
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
NORDIN JOEL 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 客員研究員 (70836064)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | extracellular vesicles / Syn-Notc |
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| Outline of Annual Research Achievements |
Chimeric antigen receptor T-cell (CAR T) therapies have gained momentum. However, CAR T cells have limitations; they can only respond with a T-cell response, they are affected by the tumour microenvironment and can easily be exhausted. Recently, a new concept has been developed with Synthetic Notch (Syn-Notch) receptors, which allow direct transcriptional control of genes of interest when the receptor is activated. The recognition domain has further been altered to a single-chain variable fragment (scFv) or peptide to allow for target recognition. Up to date, the Syn- Notch cells have merely been capable of secreting therapeutic proteins into the extracellular space, such as antibodies and cytokines. Here, we utilised engineered extracellular vesicles (EVs) to deliver macromolecular drugs into recipient cells after Syn-Notch activation. EVs have been shown to be able to transfer macromolecules between cells, which has been utilised in therapeutic settings. This would permit the Syn-Notch cells to deliver therapeutically active macromolecules such as proteins and RNAs to the cytoplasm of recipient cells and overcome limitations of EV- and CAR T cell-based therapies simultaneously. This would also increase the druggable targets since all proteins and RNAs are possible targets.
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