Development of a new treatment method against renal cancer using immune checkpoint inhibitors

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670703
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Kyushu University (2015); Kumamoto University (2014)
• Principal Investigator: Eto Masatoshi 九州大学, 医学(系)研究科(研究院), 教授 (90315078)
• Co-Investigator(Kenkyū-buntansha): MOTOSHIMA Takanobu 熊本大学, 医学部附属病院, 医員 (60726355)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 癌 / 免疫学

Outline of Final Research Achievements

Recently, molecular targeted drugs including tyrosine kinase inhibitors (TKIs) and mTOR inhibitors have clearly prolonged overall survival of patients with metastatic RCC (mRCC). However, we have already known their limitations in the treatment of mRCC. To improve the antitumor effects, we have established a murine model of renal cancer treatment where a combined treatment with a TKI, sorafenib, and an immune checkpoint inhibitor, anti-CTLA-4 mAb is performed. Two possible mechanisms have been considered. One is a blockade of negative signals via CTLA-4 molecules on T cells by anti-CTLA-4 mAb. The other is an inhibition of immune suppressive genes, such as TGF-beta and IL-10, in myeloid derived suppressor cells (MDSC) by sorafenib. We have also established a murine model of renal cancer treatment where a combination therapy of two immune checkpoint inhibitors, anti-PD1 mAb and anti-CTLA-4 mAb, is performed. A clinical application of this combination therapy is awaited.

Free Research Field

泌尿器腫瘍学