Development of gene therapy for refractory non-Hodgkin lymphoma using T-cells expressing a chimeric antigen receptor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390247
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: OZAWA keiya 自治医科大学, 医学部, 客員教授 (30137707)
• Co-Investigator(Kenkyū-buntansha): TSUKAHARA Tomonori 自治医科大学, 医学部, 講師 (10362120) ; UCHIBORI Ryousuke 自治医科大学, 医学部, 助教 (20458285) ; OHMINE Ken 自治医科大学, 医学部, 講師 (90316521)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 遺伝子治療 / 免疫療法 / 細胞療法 / キメラ抗原受容体 / Tリンパ球 / 造血器腫瘍

Outline of Final Research Achievements

Gene therapy for refractory B-cell non-Hodgkin lymphoma using T-cells expressing a chimeric antigen receptor (CAR) was studied as follows: (1) To improve the anti-tumor activity, T-cells were transduced with CD19-targeted CAR and IL-21 genes. However, the therapeutic effect was not enhanced by IL-21 in tumor-bearing mice. (2) For the safety, we developed a switch promoter, which stimulates transgene expression in CAR T-cells upon interaction with target cells. We demonstrated that this system works through CAR-dependent signaling in CAR T-cells in vitro and in tumor-bearing mice. (3) We manufactured CD19-CAR T-cells from patient-derived PBMCs by a closed cell-processing system, and confirmed that these T-cells can kill B lymphoma cells in vitro. (4) A clinical protocol (CD19-CAR T-cell therapy for B-cell lymphoma) was approved by IRB and the Ministry of Health, Labour and Welfare. Enrollment started in December 2014.

Free Research Field

遺伝子治療学、細胞治療学、血液内科学