Biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines against malignant brain tumor patients

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08951
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Keio University
• Principal Investigator: UEDA Ryo 慶應義塾大学, 医学部(信濃町), 講師 (30317143)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 悪性脳腫瘍 / 腫瘍抗原ペプチドワクチン / 脳腫瘍血管新生 / 免疫療法 / バイオマーカー

Outline of Final Research Achievements

Evaluation of immunological biomarkers may lead to better understanding of the critical immune response indicators that may help to predict clinical responses of cancer immunotherapy. We characterized status of immune cells, cytokines, chemokines, and other immunosuppressive molecules in refractory brain tumor patients who received vaccinations of VEGF receptor (VEGFR)-derived peptides. Peripheral blood samples from patients who demonstrated positive radiologic response or stable disease revealed superior VEGFR-specific CTL reactivity compared to samples from other patients with refractory brain tumors. Plasma IL-8 level was negatively correlated with overall survival. Furthermore, expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to the therapeutic efficacy VEGFR-targeted vaccines. These data indicate that these parameters may be potential immune-biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

脳腫瘍血管新生抑制療法とがんワクチン免疫療法という2つの治療要素を併せ持つ悪性脳腫瘍に対する治療はこれまでに行われておらず、本研究により、脳腫瘍微小環境の免疫学的解析や脳腫瘍患者での免疫応答、脳腫瘍血管新生機構の解明など、これまでのがん治療の臨床試験では検証されていなかった知見を、がん免疫療法や腫瘍血管新生抑制療法の改良・開発に向けた基礎研究にフィードバックし得る。また、基礎研究では判明しなかった現象が臨床試験において初めて明らかにされることもある。これらの情報は、今後の免疫的治療法・血管新生抑制療法開発にとって欠かすことができない重要な指針となり、がん医療の発展に寄与する可能性がある。