Establishment of T lymphocytes expressing chimeric antigen receptor for leukemic stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390260
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: KOIKE Kenichi 信州大学, 学術研究院医学系, 教授 (40143979)
• Co-Investigator(Kenkyū-buntansha): SAKASHITA Kazuo 信州大学, 医学部附属病院, 特任研究員 (10345746) ; NAKAZAWA Yozo 信州大学, 学術研究院医学系(医学部附属病院), 講師 (60397312)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 白血病性幹細胞 / キメラ抗原受容体T細胞 / 小児白血病 / 若年性骨髄単球性白血病 / CD34陽性細胞 / GM-CSF receptor

Outline of Final Research Achievements

We evaluated anti-proliferative potential of T cells non-virally engineered to bind to granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR.CAR T cells) against juvenile myelomonocytic leukemia (JMML) CD34+ cells. The co-culture of healthy or JMML GMR.CAR T cells with CD34+ cells of JMML patients in the presence of stem cell factor (SCF), thrombopoietin (TPO) and interleukin-3 for 2 days significantly decreased the total colony growth. Seven-day co-culture of GMR.CAR T cells with JMML CD34+ cells resulted in a marked suppression on the expansion of CD34+ cells, particularly CD34+CD38- cells, under stimulation with SCF+TPO on AGM-S3 cells. Meanwhile, GMR.CAR T cells exerted no effects on the colony growth of normal CD34+ cells. Thus, our GMR.CAR T cells may provide a novel adoptive immunotherapy for this disease.

Free Research Field

小児血液腫瘍学