Efficacy of co-stimulatory molecule CD40 against glioma stem cells; research for mechanism and combination with PD-1 inhibitor.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15301
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tohoku University
• Principal Investigator: Chonan Masashi 東北大学, 医学系研究科, 非常勤講師 (90813676)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: CD40 / OX40 / 免疫療法 / 神経膠腫

Outline of Final Research Achievements

Efficacy of immunotherapy using intravenous administration of anti-CD40 antibody in combination with intravenous administration of anti-PD-1 antibody was performed against rodent brain tumor model. Brain tumor mice were randomly assigned to 4 treatment groups; Group1 control, Group2 anti-CD40 antibody, Group 3 anti-PD-1 antibody, Group 4 combination. As a result, survival of mice in treatment groups 2 and 4, which received anti-CD40 antibody treatment, was significantly shorter than control as well as anti-PD-1 antibody group (p<0.05). In vivo imaging study performed simultaneously revealed rapid growth of tumors in group 2 and 4 confirming the result of survival study. Analysis of tumor infiltrating immune cells is now on-going. We are also planning another survival study using vaccination, i.e. subcutaneous administration of anti-CD40 antibody and/or anti-PD-1 antibody in combination with tumor lysate based subcutaneous vaccine and evaluate the difference in efficacy.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

膠芽腫を代表とした悪性神経膠腫の治療成績は、現時点での外科的摘出術、化学療法、放射線治療を用いても依然として絶対的に不良であり、第4の治療法として注目されている免疫治療の開発が急務とされている。近年、悪性神経膠腫の治療抵抗性には腫瘍幹細胞が関与しているとされ、我々は免疫共剌激因子であるCD40（樹状細胞やB細胞活性化し間接的に抗腫瘍効果を発揮するとともに、腫瘍細胞に対しては直接的にアポトーシスを誘発）の刺激抗体を用いた免疫治療の開発を目指して研究を進めている。