Development of a new CAR-NK cell therapy using activated NK cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16437
• 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: Tokyo Medical and Dental University
• Principal Investigator: KAMIYA TAKAHIRO 東京医科歯科大学, 東京医科歯科大学病院, 特任助教 (20574693)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CAR / NK細胞 / 免疫細胞療法

Outline of Final Research Achievements

In this study, we aimed to overcome the limitations of the current CAR-T cell therapy such as the one for solid tumors, by developing and improving a new CAR therapy with NK cells. First, as a system to obtain stable NK cell proliferation, we succeeded in creating a K562 cell line with forced expression of NK stimulating factors IL-15 and 41BBL on the cell surface. The cell line was purified with strong expression after single cell culture. Next, a new CAR construct for NK cells was designed and cloned. We also established cytotoxic activity assays using flow cytometry, and degranulation and intracellular cytokine assays as evaluation systems. On the other hand, stable activated NK cell culture and CAR expression could not be achieved.

Free Research Field

免疫細胞療法

Academic Significance and Societal Importance of the Research Achievements

今回得られたNK細胞活性化細胞株や、免疫細胞の活性化を評価する指標としての細胞障害活性、サイトカイン産生能、脱顆粒能の測定系の確率は、CAR細胞療法に限らず様々な免疫細胞療法の研究に応用できる重要な成果であると考えられる。
また、安定した発現を得るに至らなかったものの、新たなCARコンストラクトの最適化により今後NK細胞を用いたCAR研究が広がるものと期待される。