Immunotherapy with HDAC inhibitor against malignant glioma

2015 Fiscal Year Final Research Report

• Project/Area Number: 23592137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Yokohama City University
• Principal Investigator: SATO Hidemitsu 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (70363801)
• Co-Investigator(Kenkyū-buntansha): KANNO Hiroshi 横浜市立大学, 医学研究科, 客員准教授 (40244496)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Keywords: gliioblastoma / immunotherapy / HDAC inhibitor / MGMT promotor / temozolomide / valproate

Outline of Final Research Achievements

Valproate(VPA) is an anti-epileptic agent with abilities of a histone deacetylase inhibitor (HDACi) which enhances immune response. Recent studies suggest that VPA is associated with improved survival in glioblastomas (GBMs). We examined the immunological mechanisms of VPA against GBMs. VPA emphasized the cytotoxic activity against GBM cell line by stronger expression of immune related surface markers like major histocompatibility complex (MHC) class I resulted in enhanced expression of glioma antigens.
Moreover, we examined the influence of VPA against the methylation of O6-methylguanin-DNA-methyltransferase (MGMT) promotor by pyrosequence analysis. In our study, VPA did not have adverse influence of temozolomide resistant activity in GBMs.　Taken together, we suggested that VPA might be recommended to use for combined therapy of temozolomide and immunotherapy against GBMs.

Free Research Field

脳神経外科学