Development of the novel gene-immunotherapy using artificial CTL targeting leukemia stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390245
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: YASUKAWA Masaki 愛媛大学, 医学(系)研究科(研究院), 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): 2012-04-01 – 2015-03-31
• Keywords: 白血病 / がん免疫療法 / 細胞傷害性T細胞 / T細胞レセプター / 遺伝子治療

Outline of Final Research Achievements

We performed the series of experiment in order to establish the novel gene-immunotherapy targeting leukemia stem cells. WT1-TCR-gene-transduced CTLs exerted cytotoxicity against leukemia cells but not normal cells. It was strongly suggested that leukemia stem cells might be eliminated completely by administration of WT1-TCR gene-modified T cells. WT1-specific and HLA-restricted CTLs could be generated in HLA-TG-NSG mice by transplantation of WT1-TCR gene-transduced human hematopoietic stem cells. CD16-CD3ζ chimeric antigen receptor gene-modified CD8+ T cells showed strong ADCC activity in the presence of anti-CD20 monoclonal antibody targeting malignant lymphoma cells. 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