Research for the way to enhance the infiltration of tumor antigen specific CTLs into tumors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16863
• 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: Nakata Jun 大阪大学, 医学系研究科, 助教 (90528952)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: WT1 / ペプチドワクチン療法 / ヘルパーペプチド

Outline of Final Research Achievements

Both depletion of CD4+ T cells and combination of helper peptide vaccination could enhance the induction of WT1-specific CTL response in periferal bloods by WT1-CTL peptide vaccination. But, the frequency of WT1-specific CTLs did not increase by the depetion of CD4+ T cells. On the contrary, combination of WT1 helper peptide could induced higher frequencies of WT1-specific CTL response than WT1-CTL peptide vaccination alone. There results suggested that WT1 specific CD4+ T cells were essential to enhance the anti-tumor WT1-CTL response by WT1-CTL peptide vaccination. Furtheremore, we identified the array of T cell receptor of intra-tumoral WT1-specific CTLs, and named as 1B10-TCR. We also established virus vector which could induce 1B10-TCR.

Free Research Field

癌免疫

Academic Significance and Societal Importance of the Research Achievements

CD4+T細胞にはCTLの活性・抑制の2面性が報告されてきたが、腫瘍内に癌抗原特異的CTLを効果的に誘導するためにはヘルパーペプチドCD4+T細胞が必要不可欠であることを明らかにした。本知見は今後癌ワクチン療法の開発において進むべき道を明確にした。また、ヘルプ活性の高い外来性抗原由来のCD4+T細胞は末梢血中では強い誘導を引き起こしたが、腫瘍内への癌抗原特異的CTL誘導では癌抗原特異的ヘルパーペプチドが有意に増強効果がすぐれており、腫瘍内の免疫環境においてCD4T細胞-樹状細胞-CD8T細胞の複合体の形成が効果的な抗腫瘍免疫の誘導に必要である可能性が示唆された。