The development of immunotherapy in malignant brain tumor to overcome cancer immunosuppression and immune evasion

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861270
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Ohno Masasuke 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (40402606)
• Co-Investigator(Renkei-kenkyūsha): NATSUME Atsushi 名古屋大学, 医学系研究科, 准教授 (30362255)
• Research Collaborator: OKADA Hideho ピッツバーグ大学, 脳神経外科, 教授 ; KURAMITSU Shunichiro 名古屋大学, 医学系研究科 ; SHIINA Satoshi 名古屋大学, 医学系研究科
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: cancer immunotherapy / CAR / glioblastoma / immunomodulatory drug / gene therapy / micro RNA

Outline of Final Research Achievements

Glioblastoma (GBM) is the most lethal malignant brain tumor in adults despite the improvement on outcomes with this combined chemoradiotherapy approach after maximal surgical resection. In recent years, immunotherapy has emerged as a promising strategy for the treatment of GBM, especially CAR T-cell therapy is considered to be the most promising method to cure cancer. Chimeric antigen receptor (CAR)-transduced T cells can recognize pre-defined tumor surface antigens independent of MHC restriction, which is often downregulated in GBM. We constructed several CARs that recognize antigens expressing on the surface of GBM cells. We also developed new combination therapies to overcome cancer immunosuppression and immune evasion. Additional gene therapy or immunomodulatory drug therapy showed marked improvements in the survival time of the mice models of GBM.

Free Research Field

Neurooncology