Development of a new strategy for cancer therapy based on RIG-I and MAVS signaling pathway
| Project/Area Number |
16H04712
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
種村 篤 大阪大学, 医学系研究科, 講師 (50457016)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 抗腫瘍免疫 / がん / 癌 / 免疫学 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus2019
Author(s)
Shimbo, T., Endo, M., Iwai; S., Kitayama, T., Ouchi, Y., Yamamoto, R., Takaki, E., Yamazaki, S., Nishida, M., Wang, X., Kikuchi, Y., Tomimatsu, T., Kaneda, Y., Kimura, T. Tamai, K
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Journal Title
Biochemical and Biophysical Research Communications
Volume: pii: S0006-291X(19)
Issue: 2
Pages: 30410-3
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.2018
Author(s)
Mitsuda Y, Morita K, Kashiwazaki G, Taniguchi J, Bando T, Obara M, Hirata M, Kataoka TR, Muto M, Kaneda Y, Nakahata T, Liu PP, Adachi S, Sugiyama H, Kamikubo Y.
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Journal Title
Sci. Rep.
Volume: 8
Issue: 1
Pages: 6423-6423
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phase I/II clinical trial to assess safety and efficacy of intratumoral and subcutaneous injection of HVJ-E to castration resistant prostate cancer patients.2017
Author(s)
Fujita, K., Nakai, Y., Kawashima, A., Ujike, T., Nagahara, A., Uemura, M., Miyagawa Y., Lee, C-M., Inoue, T., Kaneda, Y., Nonomura, I.
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Journal Title
Cancer Gene Therapy
Volume: 24
Issue: 7
Pages: 277-281
DOI
Related Report
Peer Reviewed / Open Access
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