Development of a novel chimeric antigen receptor gene-modified T cell therapy targeting GD2 for neuroblastoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya University
• Principal Investigator: Nishio Nobuhiro 名古屋大学, 医学部附属病院, 特任講師 (00586430)
• Co-Investigator(Kenkyū-buntansha): 高橋 義行 名古屋大学, 医学系研究科, 教授 (40432273)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経芽腫 / GD2 / CAR

Outline of Final Research Achievements

In this study, in order to develop a new treatment for neuroblastoma, the most common solid tumor among pediatric cancers other than brain tumors, with fewer side effects, we generated a new chimeric antigen receptor CAR targeting GD2 expressed on the cell surface of neuroblastoma cells and used a piggyBac transposon gene transfer method with low production cost. CAR-T cell therapy for neuroblastoma. Multiple GD2.CAR-T cells could be generated by combining multiple antigen recognition sites and co-stimulatory molecules and optimizing the culture method. Functional analysis was performed, and it was possible to select GD2.CAR-T cells with potent tumor cell injury, low exhaustion, and good cell proliferation.

Free Research Field

小児がん、免疫療法

Academic Significance and Societal Importance of the Research Achievements

本研究において神経芽腫に対する最適化されたGD2.CAR-T細胞療法への基盤構築ができたため、実用化されれば致死的な再発・難治神経芽腫の予後が改善することが期待される。piggyBacトランスポゾン遺伝子導入法を用いたCAR-T細胞はウイルスベクター法と比較して製造コストが低く、GD2陽性小児腫瘍や他の癌種に対するCAR-T療法開発への波及効果も期待出来る。