Therapeutic employment of leukemia-reactive CD4-CD8 T-cell network aiming at improved clinical efficacy.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: Fujiwara Hiroshi 愛媛大学, 医学部附属病院, 講師 (20398291)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 遺伝子細胞免疫療法 / 遺伝子改変T細胞 / T細胞受容体遺伝子 / キメラ型抗原受容体遺伝子 / 白血病幹細胞 / 抗腫瘍性T細胞ネットワーク / 免疫記憶細胞

Outline of Final Research Achievements

Aiming at a clinically effective gene-modified T-cell based adoptive immunotherapy against human leukemias, we multilaterally studied the leukemia reactive T-cell network comprising leukemia stem cell reactive T-cell receptor (TCR) gene modified CD8 killer T cells and CD4 helper T cells, targeting Wilms Tumor 1 (WT1) and Aurora Kinase A (AURKA).This study included a unique HLA class I restricted TCR gene-modified CD4 T cells and autologous transplantation using WT1-specific TCR gene-modified hematopoietic stem cells. In parallel, we conducted a clinical trial.
Additionally, we also have developed a novel chimeric antigen receptor (CAR) gene-modified T cells, expressing affinity-increased CD16 which can employ anticancer monoclonal antibodies for target recognition, e.g., mogamulizumab against adult T cell leukemia. Furthermore, we are now developing a novel CAR gene which can recognize an epitope/HLA complex derived from cytoplasmic cancer antigens like as TCR-T cells.

Free Research Field

血液内科学、腫瘍免疫学、感染免疫学、造血幹細胞移植