The development of combination therapy of WT1 peptide vaccine with immune checkpoint inhibitors against glioma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Osaka University
• Principal Investigator: Takano Koji 大阪大学, 医学系研究科, 招へい教員 (90649203)
• Research Collaborator: Yokota Chisato
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: WT1 / ペプチドワクチン / 免疫療法 / 免疫チェックポイント阻害剤 / 神経膠腫 / 免疫逃避 / PD-1 / PD-L1

Outline of Final Research Achievements

We analyzed specimens taken from the clinical trial for WT1 peptide vaccine against glioma.The down regulation of WT1 gene product and HLA class 1 as well as the reduction of tumor-infiltrating CD4+ cells were thought to be involved in tumor tolerance against WT1 peptide vaccine.
In the animal experimentation with mouse glioma model, the combination group treated with WT1 peptide vaccine and anti PD-1 antibody showed significantly prolonged survival time comparing with the control group, WT1 peptide vaccine group or anti PD-1 antibody group.
FACS analysis revealed that WT1 peptide vaccine enhanced the effect of anti PD-1 antibody through changing tumor microenvironment such as increment of tumor infiltrating lymphocyte and decrement of MDSC.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

神経膠腫は他のがんと比較しても予後不良な疾患であり、有効な治療法が乏しい。しかも他のがんに比し若年者に多く、早期から麻痺や高次脳機能障害による生活自立度の低下が認められるため、社会的な影響も大きい疾患である。本研究を通して、動物実験レベルではあるが、神経膠腫に対するWT1ペプチドワクチン・免疫チェックポイント阻害剤併用療法の有効性を示し、その作用機序の一端を明らかにすることができた。臨床試験などさらなる研究が必要ではあるが、今後、神経膠腫に対する新たな有効な治療法の確立が期待される。