gene introduction using myeloid lineage cells

• Project/Area Number: 16K14634
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Teikyo University
• Principal Investigator: Shirafuji Naoki 帝京大学, 医学部, 教授 (00206301)
• Research Collaborator: Tashiro Haruko 帝京大学, 医学部, 講師
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: CD34 / CD47 / 造血幹細胞 / 遺伝子導入 / CAR-T / PBSCT / G-CSF / CLL-1 / CD19 / 遺伝子運搬 / 好中球 / 抗腫瘍効果 / 骨髄芽球

Outline of Final Research Achievements

We constructed shuttle vector that expressed antisense nad miRNA RNA for human CD47. This vector was introduced into CD13 and CD33-positive bone marrow mononuclear cell fractions which was isolated with magnetic beads. The positive cell-fraction was cultured with recombinant human granulocyte colony-stimulating factor. The obtained mature neutrophilic granulocytes expressed anti CD47 antisense RNA and miRNA. Biological antitumor effects were also elevated.

Research Products

• [Journal Article] Direct Factor X sequestration by systemic amyloid lightchain amyloidosis (2018)
  • Author(s): Haruko Tashiro, Ryosuke Shirasaki, Masato Watanabe, Kazuo Kawasugi, Yoshihisa Takahashi, Naoki Shirafuji
  • Journal Title: Clinical Case Reports Volume: 6(3): Issue: 3 Pages: 513-515
  • DOI: 10.1002/ccr3.1398
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aggressive NK Cell Leukemia with Hemophagocytic Lymphohistiocytosis: A Case Report (2017)
  • Author(s): Kimiko Nogi, Haruko Tashiro, Kazuo Kawasugi, Mayumi Matsuzawa, Takeshi Osawa, Ryohei Toyooka, Taiji Furukawa, Naoki Shirafuji
  • Journal Title: J Clin Lab Med Volume: 2.2 Issue: 2 Pages: 1-4
  • DOI: 10.16966/2572-9578.116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunotherapy against cancer-related viruses. (2017)
  • Author(s): Tashiro H, Brenner MK
  • Journal Title: Cell Res. Volume: 27 (1) Issue: 1 Pages: 59-73
  • DOI: 10.1038/cr.2016.153
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vaccination targeting native receptors to enhance the function and proliferation of chimeric antigen receptor (CAR)-modified T cells. (2017)
  • Author(s): Tanaka M, Tashiro H, Omer B, Lapteva N, Ando J, Ngo M, Mehta B, Dotti G, Kinchington PR, Leen AM, Rossig C, Rooney CM.
  • Journal Title: Clin Cancer Res. Volume: 23 Issue: 14 Pages: 3499-3509
  • DOI: 10.1158/1078-0432.ccr-16-2138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells. J Immunol. 2017 May 26. pii: 1601494. doi: 10.4049/jimmunol.1601494. (2017)
  • Author(s): Schmueck-Henneresse M, Omer B, Shum T, Tashiro H, Mamonkin M, Lapteva N, Sharma S, Rollins L, Dotti G, Reinke P, Volk HD, Rooney CM.
  • Journal Title: J Immunol. pii: 1601494. Volume: 199(1) Issue: 1 Pages: 348-362
  • DOI: 10.4049/jimmunol.1601494
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma. (2017)
  • Author(s): Heczey A, Louis CU, Savoldo B, Dakhova O, Durett A, Grilley B, Liu H, Wu MF, Mei Z, Gee A, Mehta B, Zhang H, Mahmood N, Tashiro H, Heslop HE, Dotti G, Rooney CM, Brenner MK.
  • Journal Title: Mol Ther. Volume: 25(9) Issue: 9 Pages: 2214-2224
  • DOI: 10.1016/j.ymthe.2017.05.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Treatment of acute myeloid leukemia with T cells expressing chimeric antigen receptors directed to C-type lectin-like molecule 1. (2017)
  • Author(s): Tashiro H, Sauer T, Shum T, Parikh K, Mamonkin M, Omer B, Rouce R, Lulla P, Rooney C, Gottschalk S, Brenner MK. Treatment of acute myeloid leukemia with T cells expressing chimeric antigen receptors directed to C-type lectin-like molecule 1.
  • Journal Title: Mol Ther. Volume: 25 (9) Issue: 9 Pages: 2202-2213
  • DOI: 10.1016/j.ymthe.2017.05.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevated level of serum antinuclear antibody and hemophagocytic syndrome in Asian-variant intravascular large B-cell lymphoma: a case report with its diagnostic pitfalls. (2016)
  • Author(s): Kikuchi Y, Ota Y, Matsuo T, ShirafujiN, Kondo F, Uozaki H
  • Journal Title: Int J Clin Exp Pathol. Volume: 9 Pages: 7739-7743
• [Presentation] IL-1-βと電気刺激による成人ヒト皮膚線維芽細胞のhemogenic endotheliumへの変化に関する研究 (2018)
  • Author(s): 白藤 尚毅,松尾 琢二,住吉 立,田代 晴子
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] 赤血球抗原情報検索システムの有用性と問題点について (2017)
  • Author(s): 灰野夏澄、前島理恵子、藤原孝記、冨山秀和、金子 強、永友ひとみ、蟹井はるか、笠井英利、難波宏美、大曽根和子、松本謙介、白藤尚毅。
  • Organizer: 第65回日本輸血・細胞治療学会（6月、千葉）
• [Presentation] ABO不適合臍帯血移植後のドナー由来赤血球抗原量の解析 (2017)
  • Author(s): 蟹井はるか、藤原孝記、前島理恵子、冨山秀和、灰野夏澄、金子 強、永友ひとみ、笠井英利、難波宏美、大曽根和子、松本謙介、白藤尚毅。
  • Organizer: 第65回日本輸血・細胞治療学会（6月、千葉）
• [Presentation] 好中球増多を伴った多発性骨髄腫の１例。 (2017)
  • Author(s): 芳賀、幸、松本謙介、住吉 立，松尾 琢二，山本 義，白崎良輔、田代晴子、大井 淳，白藤尚毅、滝川 一。
  • Organizer: 第633回日本内科学会関東地方会 (6月、東京)
• [Presentation] 全身性アミロイドーシスによる高度の第X因子欠乏を来したB細胞性リンパ増殖性疾患 (2017)
  • Author(s): 田代晴子、住吉 立，松尾 琢二，山本 義，松本謙介、大井 淳，秋山 暢，川杉 和夫，白藤尚毅。
  • Organizer: 第7回日本血液学会関東甲信越地方会（7月、松本）
• [Presentation] FLT3-ITD mutation in MDS onset is associated with early transformation to AML (2017)
  • Author(s): Ritsu Sumiyoshi, Tadashi Yamamoto, Takuji Matsuo, Yoko Oka-Miura, Haruko Tashiro, Kensuke Matsumoto, Jun Ooi, Naoki Shirafuji.
  • Organizer: 78回日本血液学会総会（10月、横浜）
  • Int'l Joint Research
• [Presentation] Low HDL is a significant poor prognostic factor in malignant lymphoma (ML) (2017)
  • Author(s): Takuji Matsuo, Ritsu Sumiyoshi, Tadashi Yamamoto, Haruko Tashiro, Kensuke Matsumoto, Jun Ooi, Nobu Akiyama, Kazuo Kawasugi, Naoki Shirafuji.
  • Organizer: 78回日本血液学会総会（10月、横浜）
  • Int'l Joint Research
• [Presentation] Perkinson’s disease (PD) developed after Bortezomib (Bor)-containing chemotherapy for Mantle cell lymphoma (MCL) (2017)
  • Author(s): Yoko Miura, Takuji Matsuo, Ritsu Sumiyoshi, Tadashi Yamamoto, Haruko Tashiro, Kennsuke Matsumoto, Jun Ooi, Naoki Shirafuji.
  • Organizer: 78回日本血液学会総会（10月、横浜）
  • Int'l Joint Research
• [Presentation] Primary Adrenal Lymphoma with Adrenal Insufficiency: Report of Three Cases and Review of Literature (2017)
  • Author(s): Masumi Ogawa, Naoki Edo, Takuji Matsuo, Tadashi Yamamoto, Satoshi Takahashi, Yamato Mashimo, Koji Morita, Yuko Sasajima, Hiroshi Uozaki, Fukuo Kondo, Yasunori Ota, Naoki Shirafuji, Hiroko Okinaga, Kazuhisa Tsukamoto, Toshio Ishikawa.
  • Organizer: ENDO 2017 (April, Orlando, Florida USA)
  • Int'l Joint Research
• [Presentation] Constitutive Signaling from an Engineered IL-7 Receptor Promotes Durable Tumor Elimination by Tumor Redirected T-Cells (2017)
  • Author(s): Thomas Shum, Bilal Omer, Haruko Tashiro, Robert Kruse, Dimitrios Wagner, Kathan Parikh, Zhongzhen Yi, Tim Sauer, Robin Parihar, Leonid Metelitsa, Stephen Gottschalk, Cliona Rooney
  • Organizer: ASGCT 20th Annual Meeting (May, Washington DC, USA)
  • Int'l Joint Research
• [Presentation] A Single CRISPR-Mediated Knockout as Novel Suicide Switch and Selection Tool for Gene-Modified T Cells (2017)
  • Author(s): Dimitrios L. Wagner, Haruko Tashiro, Thomas Shum, Debopriyo Halder, Michael C. Gundry, Lorenzo Brunetti, Ciaran M. Lee, Benjamin H. Shin, Tim Sauer, Maksim Mamonkin, Gang Bao, Margaret A. Goodell, Cliona M. Rooney
  • Organizer: ASGCT 20th Annual Meeting (May, Washington DC, USA)
  • Int'l Joint Research
• [Presentation] Low high-density lipoprotein cholesterol (HDL) is a significant poor prognostic factor in malignant lymphoma (2017)
  • Author(s): Takuji Matsuo, Haruko Tashiro, Ritsu Sumiyoshi, Tadashi Yamamoto, Yoko Oka-Miura, Kensuke Matsumoto, Jun Ooi, Naoki Shirafuji
  • Organizer: 59th ASH meeting (December, Atlanta, Georgia, USA,)
  • Int'l Joint Research
• [Presentation] FLT3-ITD mutation in MDS patients is associated with early transformation to AML (2017)
  • Author(s): Ritsu Sumiyoshi, Haruko Tashiro, Takuji Matsuo, Tadashi Yamamoto, Yoko Oka-Miura, Kensuke Matsumoto, Jun Ooi, Naoki Shirafuji.
  • Organizer: 59th ASH meeting (December, Atlanta, Georgia, USA,)
  • Int'l Joint Research
• [Presentation] Biological effect of IL-1-beta to HDF for a long-term culture (2016)
  • Author(s): Ritsu Sumiyoshi, Takuji Matsuo, Ryosuke Shirasaki, Yoko Oka-Miura, Tadashi Yamamoto, Kennsuke Matsumoto, Jun Ooi, Nobu Akiyama, Kazuo Kawasugi, Naoki Shirafuji.
  • Organizer: 77th JSH
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2016-10-13
• [Presentation] Outcome of salvage chemotherapy against relapsed or refractory advanced non-Hodgkin’s lymphoma cases (2016)
  • Author(s): Takuji Matsuo, Ritsu Sumiyoshi, Tadashi Yamamoto, Kennsuke Matsumoto, Jun Ooi, Nobu Akiyama, Kazuo Kawasugi, Naoki Shirafuji.
  • Organizer: 77th JSH
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2016-10-13
• [Presentation] Vascular endothelial cell-relating molecules expressed in an adult human dermal fibroblast when cultured with interleukin-1-beta (2016)
  • Author(s): Rhitsu Sumiyoshi, Takuji Matsuo, Tadashi Yamamoto, Kennsuke Matsumoto, Jun Ooi, Kazuo Kawasugi, Naoki Shirafuji.
  • Organizer: EHA
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-06-09