CAR-T therapy targeting TSLP signaling in microenvironment of lung cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16132
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Shibuya Risa 東北大学, 医学系研究科, 助教 (90778408)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 肺癌 / CAR-T療法 / 癌微小環境 / TSLP

Outline of Final Research Achievements

A CAR vector targeting lung cancer surface antigen Axl was prepared and transfected into Jurkat cells. 80-98% of the CAR expression on Jurkat cells was confirmed by flow cytometer. The activation of Axl-CAR Jurkat cells by Axl protein was also confirmed by flow cytometer.
However, the expression of TSLP in A549 and lung cancer tissues from patients were not detected. Therefore, we are focusing on cytokine signals other than TSLP, and are working on generation of Axl-CAR-T cells targeting these signals.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

CAR-T療法の固形がんへの応用は、がん免疫及び細胞移入療法の分野において現在注目を集めている。これまで、固形がんのCARのターゲット分子の探索や、がん微小環境に耐性なCARが開発されてきたが、固形がん治療でのCAR-T療法の有効性は確立されていない。本研究では、未だ明らかでないがん微小環境でのTSLPの役割に着目し、「がん微小環境の免疫抑制シグナルに負けない」CAR-T細胞の作成を目指す。本研究で期待する結果が得られた場合、肺がんを含む固形がんに対する新たなCAR-T療法として、臨床応用へ繋がる可能性が非常に高い。