Preclinical evaluation of the antitumor effect of cancer immunotherapy augmented by antiangiogenic agent in malignant pleural mesothelioma

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17654
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Negi Yoshiki 兵庫医科大学, 医学部, 助教 (70814515)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 悪性胸膜中皮腫 / 抗PD-1抗体 / 血管新生阻害薬 / がん免疫療法

Outline of Final Research Achievements

Malignant pleural mesothelioma is refractory malignant neoplasm with extreme poor prognosis. Recently, anti-programmed cell death (PD)-1 antibody, nivolumab, has been approved for the treatment of relapsed-MPM, and actually exerts remarkable antitumor effect in certain cases. Thus, anticancer immunotherapy is expected to be a breakthrough therapy in MPM as well as lung cancer.
In the present study, we established mouse subcutaneous MPM xenograft model and showed that antiangiogenic agent, nintedanib, enhanced antitumor immunity against MPM cells induced by anti PD-1 antibody via through activating cytotoxic T cell not only numerically but also functionally. These results indicate that antiangiogenic agent is a promising candidate as a novel molecular targeted therapy in MPM.

Free Research Field

胸部悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

悪性胸膜中皮腫は稀少がんの一種ではあるが、本邦における過去のアスベスト使用状況から今後も患者数、死亡者数は増加すると予想されている。2018年に世界に先駆けて免疫チェックポイント阻害薬ニボルマブが、再発悪性胸膜中皮腫に保険適応となった。がん免疫療法が今後の中皮腫治療の軸となっていくと予想され、その効果をどうすれば高める事ができるかを検討する事は非常に重要である。申請者は血管新生阻害薬と免疫チェックポイント阻害薬の併用が従来の免疫チェックポイント阻害薬単剤での効果を上回る可能性がを見出した。今回使用した血管新生阻害薬は実臨床で用いられており、速やかに臨床試験等の計画・実行につながる。