a novel adoptive T cell therapy exerting ADCC for pediatric cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461561
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hirosaki University
• Principal Investigator: Kudo Ko 弘前大学, 医学部附属病院, 助教 (20455728)
• Co-Investigator(Renkei-kenkyūsha): ITO Etsuro 弘前大学, 大学院医学研究科, 教授 (20168339)
• Research Collaborator: Dario Campana National University of Singapore, Department of Pediatrics
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 抗体依存性細胞障害 / 免疫療法 / 小児がん / 抗体療法

Outline of Final Research Achievements

We had already developed chimeric receptor called CD16V-BB-zeta that exerts antibody dependent cellular cytotoxicity (ADCC) in combination with therapeutic antibodies. The aim of this study was to develop a novel adoptive T cell therapy that improve ADCC using genetically modified chimeric receptor with additional signaling. We generated a new chimeric receptors consisting two signaling molecules of CD3 zeta and Fc epsilon RI gamma to improve ADCC. We transduced this receptor to activated primary T cells and evaluated if additional signaling of Fc epsilon RI gamma improve ADCC. However, no additional improvement was detected on both cytotoxicity and cell proliferation. We also checked if drug administration improve ADCC, which was exerted by CD16V-BB-zeta transduced T cells combined with therapeutic antibodies. Although drug treatment including HDAC inhibitors demonstrated upregulation of tumor specific antigen, no additional cytotoxicity was detected.

Free Research Field

小児血液腫瘍学