Novel therapeutic approach for glioblastoma with iPS cells-derived CAR-T cells

• Project/Area Number: 16K20022
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Nara Medical University
• Principal Investigator: Nakzawa Tsutomu 奈良県立医科大学, 医学部, 研究員 (00772500)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子免疫細胞治療 / CAR / 膠芽腫 / iPS細胞 / T細胞

Outline of Final Research Achievements

In this study, we aim to establish EGFRvIII-specific CAR (EvCAR)-expressing iPS cells and differentiate into T cells from the EvCAR-iPS cells. The EvCAR-expressing iPS cells were established by transducing EvCAR gene-carrying lentivirus into iPS cells. Hematopoietic stem cells (HSC) were induced from the EvCAR-iPS cells in the presence of the defined cytokines under the feedeless condition. CD3 positive and EvCAR positive cells were induced from the HSC in the presence of the defined cytokines on OP9Δ1 cells.
In conclusion, we can induce the iPS cell-derived EvCAR-T cells in vitro. The EvCAR-T cells can be a promising anti-tumoral cell source for glioblastoma if their anti-tumor effects for glioblastoma are able to be evaluate.

Research Products

• [Journal Article] Minodronic Acid in Combination with γδT Cells Induces Apoptosis of Non-small Cell Lung Carcinoma Cell Lines. (2016)
  • Author(s): Yasukawa M, Nakazawa T, Kawaguchi T, Kawai N, Tsujimura T, Tojo T, Taniguchi S.
  • Journal Title: Anticancer Research Volume: 36 Pages: 5883-5886
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo. (2016)
  • Author(s): Nakazawa T, Nakamura M, Matsuda R, Nishimura F, Park YS, Motoyama Y, Hironaka Y, Nakagawa I, Yokota H, Yamada S, Tamura K, Takeshima Y, Omoto K, Tanaka Y, Ouji Y, Yoshikawa M, Tsujimura T, Nakase H.
  • Journal Title: J Neurooncol Volume: 129 Issue: 2 Pages: 231-241
  • DOI: 10.1007/s11060-016-2186-x
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-Inhibition Effect of Levetiracetam in Combination with Temozolomide in Glioblastoma Cells (2016)
  • Author(s): Marutani A., Nakamura M., Nishimura F., Nakazawa T., Matsuda R., Hironaka Y., Nakagawa I., Tamura K., Takeshima Y., Motoyama Y., Park Y-S, Ouji Y., Yoshikawa M., Nakase H.
  • Journal Title: Neurochemical Journal Volume: Volume10, No4 Issue: 1 Pages: 333-339
  • DOI: 10.1134/s1819712416040073
  • Peer Reviewed / Open Access
• [Presentation] Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells, in human glioblastoma in vitro and in vivo (2018)
  • Author(s): Tsutomu Nakazawa, Mitsutoshi Nakamura, Ryosuke Matsuda, Fumihiko Nishimura, Young Soo Park, Yasushi Motoyama, Ichiro Nakagawa, Hiroshi Yokota, Shuichi Yamada, Kentaro Tamura, Yasuhiro Takeshima, Kouji Omoto, Yoshitaka Tanaka, Youichi Shida, Toshiharu Murakami, Rieko Takanabe, Takahiro Tsujimura, Hiroyuki Nakase
  • Organizer: The AACR Special Conference on Immunobiology of Primary and Metastatic CNS Cancer
• [Presentation] 高純度NK細胞を用いた膠芽腫細胞に対する抗腫瘍効果とTMZを用いた 併用効果の基礎的検討 (2017)
  • Author(s): 田中 祥貴, 中澤 務, 中村 光利, 辻村 貴弘, 竹島 靖浩, 松田 良介, 田村 健太郎, 山田 修一, 中川 一郎, 西村 文彦, 横田 浩, 本山 靖, 朴 永銖, 中瀬 裕之
  • Organizer: 第14回日本免疫治療学研究会学術集会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター
  • Year and Date: 2017-02-11