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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥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。

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus (2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [Presentation] Development of a novel anti-cancer immunotherapy using HVJ-E (2018)
  • Author(s): 金田安史
  • Organizer: 第56回日本癌治療学会学術集会
  • 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
• [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
• [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
  • 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
  • Invited