Developing CAR T cells for relapsed/refractory T-cell acute lymphoblastic leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: Nakazawa Yozo 信州大学, 学術研究院医学系, 教授 (60397312)
• Co-Investigator(Kenkyū-buntansha): 中野 茂 信州大学, 医学部附属病院, 特任研究員 (30791313)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: CAR-T細胞 / キメラ抗原受容体 / T細胞性腫瘍 / 急性リンパ性白血病

Outline of Final Research Achievements

Patients with relapsed or refractory (r/r) T-cell lymphoblsatic leukemia (T-ALL) have a very poor prognosis. To develop an innovative therapy for r/r T-ALL, we designed a novel chimeric antigen receptor (CAR) targeting an antigen on T cells, confirming the effective cytotoxicity of the CAR-modified T cells against a T-ALL cell line in vitro. Additionally, to determine a optimal route of administration of CAR T cells for treatment of patients with central nervous system relapse (CNS) of ALL, we established a xenograft mouse model with isolated CNS ALL. Using the in vivo model, we found that the intrathecal administration are more effective than the intravenous administration in CAR T cell therapy for isolated CNS ALL.

Free Research Field

小児白血病

Academic Significance and Societal Importance of the Research Achievements

白血病の中で最も再発・治療不応例の生命予後が不良であるT細胞性急性リンパ性白血病に対しては、世界的でも新薬の開発が進んでいない。その中でCAR-T細胞療法という新しい白血病治療手段を用いて、T細胞性急性リンパ性白血病に特化した治療モデルを提案できた意義はきわめて大きい。本研究成果に基づいて研究開発を進めることによって、きわめて難治な再発・治療不応T細胞性急性リンパ性白血病に対する新しい治療手段の創出が可能となる。