Development of novel immune therapy for melanoma by targeting tumor associated macrophages

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku University
• Principal Investigator: Fujimura Taku 東北大学, 大学病院, 講師 (50396496)
• Co-Investigator(Kenkyū-buntansha): 神林 由美 東北大学, 医学系研究科, 助教 (50755303)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 悪性黒色腫 / 免疫療法 / 腫瘍随伴性マクロファージ / 皮膚悪性腫瘍

Outline of Final Research Achievements

We have developed several novel systems for tumor immunology fields, especially in the areas of tumor associated macrophages. During this period, we have published 15 research studies about tumor associated macrophages. Among them, we have determined safety dose of IFN-beta in combination with anti-PD1 antibodies, which is based on the logics of tumor associated macrophages. Moreover, we also found the release of sCD163 and CXCL5 from tumor associated macrophages, which could be the biomarker for the prediction of the efficacy of anti-PD1 antibodies for the treatment of advanced, unresectable melanoma patients. Furthermore, we found that these biomarkers are also useful for the prediction of immune related adverse events in patients with melanoma who treated with anti-PD1 antibodies. According to these results, today, we have set up a clinical research for the development of optimal immune therapy using anti-PD1 antibody.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

当該研究により、ほとんど全ての皮膚悪性腫瘍において、CD163陽性腫瘍随伴性マクロファージが腫瘍間質に存在することが明らかとなった。さらに、悪性黒色腫においては、この腫瘍随伴性マクロファージ由来であるsCD163が健常人に比べて有意に上昇していること、悪性黒色腫においては抗PD1抗体の使用前後に変動し、この変動により抗PD1抗体の治療効果を予想できることが推測される基礎データを取ることができた。これらの基礎データをもとにして、臨床研究を行い、現在、国際特許１件と特願２件を確保した。今後、本データは免疫チェックポイント阻害薬の効果予測のバイオマーカーを決定するに当たり、重要なデータとなりうる。