The efficacy of WT1 protein oral cancer vaccine on the brain tumor and the analysis of tumor-infiltrating lymphocytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16384
• 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: Osaka University
• Principal Investigator: Minagawa Hikaru 大阪大学, 医学部附属病院, 医員 (60792132)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がんワクチン / 腫瘍免疫 / 腸内細菌 / ビフィズス菌 / WT1 / 脳腫瘍 / 血液脳関門 / 腫瘍内浸潤リンパ球

Outline of Final Research Achievements

Glioblastoma cells were inoculated intracranially into the mice and irradiated to disrupt the blood-brain barrier. The mice were then given oral WT1 cancer vaccine. The survival rate was 6 out of 7 mice died, and one had a healed tumor. Even in the mice that died, there was a significant improvement in survival and a trend toward tumor volume suppression. The percentage of WT1-specific cytotoxic T lymphocytes(CTLs) in CD3+CD8+ CTLs in the peripheral blood of mice was increased in the WT1 oral vaccine group. In individuals with suppressed tumor growth, the percentage of tumor-infiltrating lymphocytes was about 0.3% in the oral vaccine group without irradiation (N=6) and about 0.7% in the group with irradiation, but did not reach the target of 1-2%.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

WT1蛋白は種々の腫瘍で発現している汎腫瘍抗原である。WT1経口がんワクチンは投与方法が簡便で、腸管組織を介して全身性の免疫応答が期待できることから、がん治療の様々な場面での活躍が期待される。今回マウス脳腫瘍モデルを用いて抗腫瘍効果を検討した。脳は血液脳関門に守られた部位であり、他の腫瘍と比べ化学療法や免疫療法による治療が難しい。本ワクチンでも、末梢血中のWT1特異的CTLは増加し、放射線照射を併用することで一定の効果を認めたものの、腫瘍内浸潤リンパ球の割合は十分高いとは言えなかった。今後は他の治療法との併用、特にヘルパー機能を介した免疫賦活効果に注目し、治療効果を高めていくことを考えている。