Assessment of Delta-like 1 homolog (DLK1) expression as a therapeutic target in small cell lung cancer and its application to radioimmunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18223
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Takagi Hironori 福島県立医科大学, 医学部, 客員研究員 (90834325)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: lung cancer / DLK1 / Notch ligand / radioimmunotherapy / astatine

Outline of Final Research Achievements

In SCLC and NSCLC, 20.5% (23/112) and 16.8% (17/101) of patients respectively had DLK1-positive tumors. In NSCLC, DLK1 expression was associated with recurrence-free survival (P<0.01) but not with overall survival. In SCLC, there was no association between DLK1 expression and survival. In addition, 125I-labeled anti-DLK1 antibody specifically targeted DLK1 on human SCLC and neuroblastoma tumor cell lines. Furthermore, 125I-labeled anti-DLK1 antibody was incorporated into tumor tissue in a mouse model.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

本研究により、小細胞肺癌と非小細胞肺癌、いずれにおいてもDLK1は一定数の発現があり、新規治療法における治療標的となり得ることが明らかにされた。また、臨床的特徴として、非小細胞肺癌においては術後再発を予測する因子となる可能性が示唆された。さらに、抗DLK1抗体複合体の、腫瘍細胞への取り込みを改善させる課題はあるものの、将来、小細胞肺癌などの予後不良の悪性疾患において、DLK1は、抗DLK1抗体を用いたRadioimmunotherapyの治療標的となる可能性が示された。