Development of new engineered CAR-T cells with the ability to block immune checkpoint pathways

• Project/Area Number: 25830118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Yamaguchi University
• Principal Investigator: SAKODA Yukimi 山口大学, 医学(系)研究科(研究院), 助教 (30629754)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 免疫療法 / キメラ抗原受容体 / 免疫チェックポイント分子 / 免疫抑制シグナル

Outline of Final Research Achievements

The adoptive transfer of chimeric antigen receptor（CAR) T cells shows an　impressive clinical efficacy against　B-cell derived hematologic malignancies, while the efficacy against solid tumors have been much less encouraging. One possible explanation of its low efficacy is that solid tumor facilitates immune checkpoint pathways as an important immune resistance mechanism within the tumor microenvironment. In this study, we have shown that CAR-T cells engineered to possess the capacity to block an immune checkpoint pathway can induce strong anti-tumor responses.