Prediction of the effect of cancer treatment based on TCR repertoire and patient information

2019 Fiscal Year Final Research Report

• Project/Area Number: 17KT0053
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Osaka University
• Principal Investigator: Kaneda Yasufumi 大阪大学, 医学系研究科, 教授 (10177537)
• Co-Investigator(Kenkyū-buntansha): 武田 理宏 大阪大学, 医学部附属病院, 准教授 (70506493)
• Project Period (FY): 2017-07-18 – 2020-03-31
• Keywords: 癌 / TCR / HVJ-E

Outline of Final Research Achievements

To analyze TCR-beta chain using small number of T clls from tumor tissue, we improved the method of TCR library. Using this method, we prepared TCR genome library by collecting tumor infiltrating T cells using flow cytometer. We are analyzing TCR-beta chain information by reading genome information using new generation genome sequencer. We prepared RNA seq. library of tumor-infiltrating T cells and employed single cell RNA seq. kit to establish RNA seq. library.
For the analysis of various clinical trial data, mixed heterogeneous data mining technology is necessary. Phase II clinical trials to treat cancer patients using HVJ-E was delayed because of the conflict of study design between PMDA and the company providing with anti-PD-1 antibody. As the cancer patient samples were not obtained, we used Alzheimer's disease patient data and established the data mining technology.
HVJ-E was effective in PDX mice transplanted with anti-PD-1 antibody resistant melanoma.

Free Research Field

遺伝子治療学

Academic Significance and Societal Importance of the Research Achievements

HVJ-Eの腫瘍内投与が全身性のT細胞にどのような影響を与えるか、RNAseqと我々が開発した簡便なTCRseq法を組み合わせて解析するデータを基に、ヒトにHVJ-Eを投与した時の免疫細胞の応答を予測できるようになる。そのため、脾臓だけでなく、腫瘍や所属リンパ節も採取し、T細胞の遺伝子発現とTCRレパトアを解析することで全身のT細胞動態にHVJ-E腫瘍内投与が与える影響を明らかにする。今後、HVJ-Eの第II相試験で得られる末梢血中のCD8+細胞、CD4+細胞の解析を行い、マウスで得られたデータと比較することで、HVJ-Eによる抗腫瘍効果の機序が明らかなり、さらに癌治療効果が期待できる。