Development of GD2-directed chimeric antigen receptor-modified T cells in pediatric patients with brain tumor

• Project/Area Number: 26860789
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: HIRABAYASHI Koichi 信州大学, 医学部, 助教(特定雇用) (10645534)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: キメラ抗原受容体（CAR) / 遺伝子改変T細胞療法 / 小児脳腫瘍 / 網膜芽細胞腫 / ボリノスタット / 脳腫瘍 / GD2 / 小児 / ヒストン脱アセチル化酵素阻害薬 / 遺伝子改変T細胞 / 併用療法 / ＧＤ２ / piggyBacトランスポゾン法

Outline of Final Research Achievements

We found that pediatric brain tumors (medulloblastoma and glioblastoma) and retinoblastoma express GD2 highly. Next, we manufactured GD2-specific chimeric antigen receptor-transducted T cell (GD2 CAR-T cell) with piggyBac transposon system which is a non-viral gene transduction method. GD2 CAR T cell killed GD2-positive tumor cell lines dramatically in vitro. We searched combination drugs to enhance the antirtumor ability of the GD2 CAR T cell. We found that histone deacetylase inhibitors, vorinostat, can enhance the antitumor ability of the GD2 CAR T cell.

Research Products

• [Journal Article] Clinical and laboratory outcomes after umbilical cord blood transplantation in a patient with mucolipidosis II alpha/beta (2016)
  • Author(s): Takumi Shibazaki, Koichi Hirabayashi, Shoji Saito, Tomonari Shigemura, Yozo Nakazawa, Kazuo Sakashita, Mineo Takagi, Masaaki Shiohara, Kaori Adachi, Eiji Nanba, Norio Sakai, Kenichi Koike
  • Journal Title: American Journal of Medical Genetics Part A Volume: 170 Issue: 5 Pages: 1278-1282
  • DOI: 10.1002/ajmg.a.37563
  • Peer Reviewed
• [Journal Article] Anaplastic Large-Cell Lymphoma of the Left Ventricle Presenting With Arrhythmia and Cerebral Infarction due to Cardiogenic Embolism (2016)
  • Author(s): Koichi Hirabayashi, Shoko Yamauchi, Satoshi Matsuzaki, Kenichi Koike, Yozo Nakazawa, Kazunori Komatsu, Kenji Sano
  • Journal Title: Pediatric Blood & Cancer Volume: 63 Issue: 4 Pages: 755-756
  • DOI: 10.1002/pbc.25859
  • Peer Reviewed
• [Journal Article] Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction. (2016)
  • Author(s): Hirabayashi K, Kurata T, Horiuchi K, Saito S, Shigemura T, Tanaka M, Yanagisawa R, Matsuda K, Sakashita K, Koike K, Nakazawa Y
  • Journal Title: Pediatr Blood Cancer Volume: 63 Issue: 4 Pages: 709-11
  • DOI: 10.1002/pbc.25819
  • Peer Reviewed / Open Access
• [Book] Wilms Tumor [Internet] (2016)
  • Author(s): Shimodaira S, Hirabayashi K, Yanagisawa R, Higuchi Y, Sano K, Koizumi T.
  • Total Pages: 294
  • Publisher: Codon Publications