Development of a novel antibody therapy based on antibody-dependent cellular cytotoxicity activity against lung cancer and mesothelioma and identification of the immunological biomarkers

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390210
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: NISHIOKA Yasuhiko 徳島大学, ヘルスバイオサイエンス研究部, 教授 (70274199)
• Co-Investigator(Kenkyū-buntansha): KATO Yukinari 東北大学, 医学(系)研究科(研究院), 教授 (00571811) ; KAKIUCHI Soji 徳島大学, 病院, 講師 (50380100) ; GOTO Hisatsugu 徳島大学, 大学院ヘルスバイオサイエンス研究部, 講師 (00437641)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 抗体療法 / ADCC / ポドプラニン / 肺癌 / 悪性胸膜中皮腫 / 免疫療法 / バイオマーカー

Outline of Final Research Achievements

We developed novel antibodies against podoplanin expressing in lung squamous cell carcinoma and mesothelioma. We generated a human-rat chimeric anti-podoplanin antibody NZ-8 which showed higher anti-tumor activity in mouse xenograft model based on antibody-dependent cellular and complement- dependent cytotoxicity as compared to those of the rat antibody NZ-1. The binding activity of NZ-8 seemed to be higher against podoplanin expressing in tumor cells rather than normal cells such as alveolar cells or podocytes, indicating the advantage for clinical use of NZ-8. We finally developed the chimeric antibody NZ-12 showing the higher anti-tumor activity than NZ-8. Furthermore, gene expression analyses in xenograft tumors treated with NZ-1 identified the candidate genes related with the biological activity of NZ-1/NZ-8.

Free Research Field

医歯薬学