Development of a novel chimeric antigen receptor T cell immunotherapy targeting immune checkpoint molecules

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09641
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Niigata University
• Principal Investigator: IMAMURA Masaru 新潟大学, 医歯学総合病院, 講師 (80464006)
• Co-Investigator(Kenkyū-buntansha): 今井 千速 新潟大学, 医歯学系, 准教授 (90419284)
• Co-Investigator(Renkei-kenkyūsha): TAKACHI Takayuki 新潟大学, 医歯学総合病院・小児科, 特任助教 (70444164)
• Research Collaborator: IWABUCHI Haruko 新潟大学, 医歯学総合病院・小児科, 医員 (60444163)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: キメラ抗原受容体 / Programmed cell death-1 / T細胞療法

Outline of Final Research Achievements

The aim of this study was to develop a novel chimeric antigen receptor T cell (CAR-T) immunotherapy targeting immune checkpoint molecules. We constructed several CARs targeting PDL1/L2 (PD1-CAR). We used extracellular domain of PD-1 from human T cell as a ligand binding domain. Various components were used in the hinge, transmembrane and intracellular domain. The CARs was retrovirally transduced into human T cells from healthy donors. PD1-CAR-T cells showed different PD-1 expression by the constructs. We stimulated OS cell line, U2OS with supernatant from co-culture of CAR-T cells and a cell line. This stimulation upregulated PD-1 ligands expression in U2OS. PD1-CAR-T cells showed significant cytotoxicity against U2OS expressing PD-1 ligands. PD1-CAR may be a candidate of a novel therapy for OS, as secondary CAR-T therapy for cancer that evade after first CAR-T cells targeting another molecule.

Free Research Field

小児血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

PDL1/L2に対する新規CAR-T細胞を作成し、その抗腫瘍効果を示すことができた。種々の構造のCAR-T 細胞を作成、検討を行い、より効果的な CAR-T 細胞による新規細胞療法を開発できた。また、悪性腫瘍細胞の PDL1/L2 はCAR-T細胞の攻撃により容易に誘導されることから、PD1-CAR-T 単独ではなく他の CAR-Tと併用することでより抗腫瘍効果を高めることができる可能性があり、今後検討していく。