Basic Research for CAR-T Therapy for Systemic Lupus Erythematosus

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20784
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Aritomi Takafumi 産業医科大学, 医学部, 非常勤医師 (20907357)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: CD11c / 全身性エリテマトーデス / CAR-T / B細胞 / T-bet / FcRL

Outline of Final Research Achievements

In this study, we aimed to investigate CAR-T therapies targeting T-bet+CD11c+ B cells to selectively regulate B cell subsets involved in SLE pathogenesis.　In silico analysis revealed that FcRL5 is expressed on a subset of B cells that we consider as targets, such as Naive B cells and DN B cells.
We have also investigated the regulatory mechanism of differentiation of T-bet+CD11c+ B cells and found that intracellular metabolism, especially enhancement of the glycolytic system, is important for the differentiation of these cells, and that the production of inflammatory cytokines such as IL-6 is important for their function.

Free Research Field

免疫

Academic Significance and Societal Importance of the Research Achievements

本研究はSLEの病態形成において大変重要な役割を果たす病的B細胞サブセットであるT-bet+CD11c+B細胞の分化機構や機能を解析し、病態解明、治療応用を目指す点で学術的意義を有する。
また、CAR-T療法の様々標的分子を対象とした治療応用や患者特性に沿った治療開発(precision medicine)の探究は、膠原病以外にも、アレルギー、癌など幅広い疾患にも応用可能であり、社会的意義が高いと考えている。