Chimeric antigen receptor T cell therapy for T cell malignancies

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16460
• 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 Cancer Center Japan
• Principal Investigator: Watanabe Keisuke 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (60847466)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ATLL / CTCL / PTCL / CCR4 / CART細胞療法 / モガムリズマブ

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATLL) is a highly resistant disease and cure is rarely achieved by standard chemotherapies. To achieve cure of ATLL by replacing allo-SCT, we developed CCR4-directed chimeric antigen receptor T cells (CART cells) by overcoming technical challenges including failure of CART cell expansion due to mutual killing of CART cells (fratricide) related with the shared antigen expression between normal T cells and tumor cells. The concept has been proven in preclinical models; CCR4CART cells were successfully established both from healthy donor and patient derived PBMCs, and administration of the CCR4CART cells induced 100% cure of xenograft mice including a mogamulizumab resistant model. These data suggested its feasibility of our CCR4CART cells to clinic.

Free Research Field

免疫療法

Academic Significance and Societal Importance of the Research Achievements

本邦は先進国で唯一のHTLV-1感染流行国で、ATLL等の関連疾患の研究や治療法開発にて世界をリードしてきた。成果としてモガムリズマブをはじめ多くの日本発の製剤が開発されたが、未だ治癒をもたらす治療法は確立していない。我々の開発したCART細胞は、従来法にない患者の治癒をもたらすもので、多くのATLL患者が恩恵を得られるとともに、本邦の国策ともいえるATLL研究に大きな影響を与えるものである。また、これまで、B細胞性血液腫瘍に対し効果が示されてきたCART細胞療法の対象を、T細胞性腫瘍に拡大するもので、免疫細胞療法開発の面でも意義が大きい。