Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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Outline of Final Research Achievements |
In the present study, we established a novel combinational immunotherapy using epitope peptide targeting glioma neoantigen and vascular endothelial growth factor receptor (VEGFR)1/2, and anti-programmed cell death (PD)-1. Induced cytotoxic T lymphocytes could kill not only tumor vessel cells but also tumor cells and immunosuppressive regulatory T cells (Tregs) expressing VEGFRs. Remarkable prolonged survival was achieved in the glioma mouse model. Furthermore, we revealed that VEGFR2 is highly expressed in the glioma stem cells (GSCs). This approach could inhibit the proliferation of GSCs in an orthotopic mouse model. The histopathological findings of pre- and post-VEGFRs vaccination glioblastoma specimens demonstrated that more apoptosis was detected in tumor cells, and the number of Foxp3-positive cells decreased after vaccination. This novel immunotherapy targeting a large variety of cells has the possibility to show higher treatment efficacy for the patients with malignant glioma.
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