Development of a new strategy for cancer therapy based on RIG-I and MAVS signaling pathway

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04712
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor therapeutics
• 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): 種村 篤 大阪大学, 医学系研究科, 講師 (50457016)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗腫瘍免疫 / がん

Outline of Final Research Achievements

The anti-tumor activity of Sendai virus envelope (HVJ-E) is dependent of RIG-I and MAVS signaling pathway, which induces anti-tumor immunity and cancer-selective cell death. We identified IRF7 plays a pivotal role for HVJ-E-activated anti-tumor activity. RNA seq. analysis was performed to elucidate gene expression pattern in melanoma samples isolated from HVJ-E-treated patients. Both T cell activation and exhaustion markers were up-regulated. Then, we obtained melanoma tissue derived from metastatic lymph node of patients resistant to anti-PD-1 therapy. PDX mice were constructed and treated with HVJ-E by intratumoral injection. Tumors were significantly suppressed by the treatment. These results suggest that combination of HVJ-E with anti-PD-1 antibody will provide more effective cancer therapy to cancer patients.

Free Research Field

腫瘍治療学

Academic Significance and Societal Importance of the Research Achievements

従来自然免疫を活性化する1つの経路を担う分子として研究されてきたRIG-Iであるが、我々は癌細胞選択的細胞死を起こすシグナルとして発見し注目してきた。今後はRIG-Iシグナルに焦点をあて癌細胞に特徴的なクロマチン構造変化やその原因究明の研究が進むことが期待され、癌細胞特異的なクロマチン構造変化を起こし細胞死を誘導できる分子機構の究明につながり、癌細胞の新たな特性を明らかにできる。本研究成果をもとにさらに研究が発展すれば、癌の予防や治療に貢献する新規標的分子の同定を可能にし、正常組織に影響を与えることなく癌を駆逐できる理想の癌治療法を提供できる。