SynNotch EV cells-flexible CAR T-cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16849
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Center of Neurology and Psychiatry
• 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)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: キメラ抗原受容体T細胞 / Synthetic Notch受容体 / 細胞外分泌小胞

Outline of Final 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.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

細胞外分泌小胞 (EV) は細胞間で高分子を移動できることが示されており、これは治療に応用されている。EVの利用により、Syn-Notch細胞が、タンパク質およびRNAのような治療に用いる高分子を受容体細胞の細胞質に送達することを可能にし、EV-およびCAR T細胞に基づく治療の制限を同時に克服する。EVはまた、多種多様のタンパク質およびRNAを送達できると考えられるため、薬物の標的を増加させうる。