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

Research Project

Project/Area Number 17KT0053
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Complex Systems Disease Theory
Research InstitutionOsaka 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords癌 / TCR / HVJ-E / 医療情報 / T細胞受容体 / 免疫 / 治験 / がん / 腫瘍免疫
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (18 results)

All 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer.2020

    • Author(s)
      Fujita K, Kato T, Hatano K, Kawashima A, Ujike T, Uemura M, Imamura R, Okihara K, Ukimura O, Miki T, Nakajima T, Kaneda Y, Nonomura N.,
    • Journal Title

      Cancer Sci.

      Volume: in press Issue: 5 Pages: 1692-1698

    • DOI

      10.1111/cas.14366

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intratumoral injection of hemagglutinating virus of Japan-envelope vector yielded an antitumor effect for advanced melanoma: a phase I/IIa clinical study.2020

    • Author(s)
      Kiyohara E, Tanemura A, Nishioka M, Yamada M, Tanaka A, Yokomi A, Saito A, Sakura K, Nakajima T, Myoui A, Sakurai T, Kawakami Y, Kaneda Y, Katayama I.
    • Journal Title

      Cancer Immunol Immunother.

      Volume: in press Issue: 6 Pages: 1131-1140

    • DOI

      10.1007/s00262-020-02509-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis.2019

    • Author(s)
      Saga K, Park J, Nimura K, Kawamura N, Ishibashi A, Nonomura N, Kaneda Y.
    • Journal Title

      J Exp Clin Cancer Res.

      Volume: 38 Issue: 1 Pages: 416-416

    • DOI

      10.1186/s13046-019-1429-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer immunotherapy using the Fusion gene of Sendai virus.2019

    • Author(s)
      Tai JA, Chang CY, Nishikawa T, Kaneda Y.
    • Journal Title

      Cancer Gene Ther.

      Volume: - Issue: 6 Pages: 498-508

    • DOI

      10.1038/s41417-019-0126-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SF3B2-mediated RNA splicing drives human prostate cancer progression.2019

    • Author(s)
      Kawamura N, Nimura K, Saga K, Ishibashi A, Kitamura K, Nagano H, Yoshikawa Y, Ishida K, Nonomura N, Kaneda Y.
    • Journal Title

      Cancer Res.

      Volume: 79 Issue: 20 Pages: 5204-5217

    • DOI

      10.1158/0008-5472.can-18-3965

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: pii: S0006-291X(19) Issue: 2 Pages: 30410-3

    • DOI

      10.1016/j.bbrc.2019.03.033

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 6423-6423

    • DOI

      10.1038/s41598-018-24969-w

    • NAID

      120006510275

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chromatin accessibility identifies diversity in mesenchymal stem cells from different tissue origins.2018

    • Author(s)
      Ho YT, Shimbo T, Wijaya E, Ouchi Y, Takaki E, Yamamoto R, Kikuchi Y,Kaneda Y, Tamai K.
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 17765-17765

    • DOI

      10.1038/s41598-018-36057-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inactivated Sendai Virus Particles upregulate cancer cell ICAM-1 expression with enhancing NK cell sensitivity on cancer cell.2017

    • Author(s)
      Simin, L., Nishikawa, T., Kaneda, Y.
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 12 Pages: 2333-2341

    • DOI

      10.1111/cas.13408

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salmonella mediated the hemagglutinating virus of Japan-envelope transfer suppresses tumor growth.2017

    • Author(s)
      Lee C-H, Nishikawa, T., Kaneda, Y.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 21 Pages: 35048-35060

    • DOI

      10.18632/oncotarget.17037

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Cancer Gene Therapy

      Volume: 24 Issue: 7 Pages: 277-281

    • DOI

      10.1038/cgt.2017.15

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cancer immunotherapy using Sendai virus envelope (HVJ-E).2019

    • Author(s)
      Kaneda Y.
    • Organizer
      国際遺伝子治療フォーラム
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HVJエンベロープベクターを用いたがん免疫治療法の開発2019

    • Author(s)
      金田安史
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of a novel anti-cancer immunotherapy using HVJ-E2018

    • Author(s)
      金田安史
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Clinical trials for the treatment of intractable cancers using HVJ envelope (HVJ-E).2017

    • Author(s)
      Kaneda, Y.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Current status and future prospect of gene therapy in Japan.2017

    • Author(s)
      Kaneda, Y.
    • Organizer
      第23回日本遺伝子細胞治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Current status and future prospect of human gene therapy.2017

    • Author(s)
      Kaneda, Y.
    • Organizer
      国際胎児新生児治療学会2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 世界の遺伝子治療の現状と展望2017

    • Author(s)
      金田安史
    • Organizer
      ,日本人類遺伝学会第62回大会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-07-21   Modified: 2021-02-19  

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