Development of novel gene-modified T cell therapy against chemotherapy-resistant leukemia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04858
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: Yasukawa Masaki 愛媛大学, 医学系研究科, 教授 (60127917)
• Co-Investigator(Renkei-kenkyūsha): 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: がん免疫療法 / 遺伝子改変T細胞 / CAR-T細胞 / T細胞レセプター / 白血病 / WT1 / NE-ESO1 / CD16

Outline of Final Research Achievements

We performed the series of experiment in order to establish the novel gene-engineered immunotherapy targeting hematological malignancies. 1) WT1-TCR-gene-transduced CTLs exerted cytotoxicity against chemotherapy-resistant leukemia stem cells. 2) CD16-CD3ζ chimeric antigen receptor gene-modified CD8+ T cells showed strong ADCC activity in the presence of monoclonal antibody targeting malignant cells. 3) HLA-A2/NY-ESO-1157 CAR-T cells appeared to exert HLA-A2-restricted cytotoxicity against hematopoietic malignancy including myeloma cells. 4) Peripheral blood CD8 T cells showed HLA-A2-restricted cytotoxicity against tumor cells in the presence of HLA-A2/NY-ESO-1157-bispecific antibody. These data strongly suggest that immunotherapy using gene-modified CTLs can establish the cure of chemotherapy-resistant hematological malignancies.

Free Research Field

血液学、感染症学、腫瘍免疫学、細胞治療