Development of novel immunocancer therapy for bladder cancer using the CD47-SIRP signaling system.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16790
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kobe University
• Principal Investigator: Sakamoto Mariko 神戸大学, 医学研究科, 医学研究員 (80834564)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: がん免疫療法 / 抗体療法 / マクロファージ

Outline of Final Research Achievements

The efficacy of anti-PD-L1 antibody against bladder cancer has already been proven. In this study, we evaluated the efficacy of anti-PD-L1 and anti-SIRPα antibody combination therapy as a cancer therapeutic agent, aiming to establish a new cancer immunotherapy against metastatic bladder cancer. The combination therapy of anti-PD-L1 and anti-SIRPα antibody enhanced the phagocytosis of macrophages against bladder cancer cells. Furthermore, a stronger tumor growth suppression effect was observed in the combination therapy group compared to the monotherapy group in tumor bearing model mice. Furthermore, analysis of immunocompetent cells in bladder tumors showed that the proportion of CD8-positive T cells which were involved in tumor elimination was increased in the combination therapy group.

Free Research Field

泌尿器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

抗PD-L1抗体と抗SIRPα抗体を併用することで、膀胱癌に対し単剤に比してより強い抗腫瘍効果を認めることができたが、併用療法による抗腫瘍効果にはマクロファージが大きく寄与しており、マクロファージのがん細胞貪食が起点となって、腫瘍内の環境が癌排除の方向へと変容し、Ｔ細胞の呼び込みに繋がっている可能性が示唆された。詳細については更なる解析が必要であるが、抗PD-L1抗体が効きにくいとされるＴ細胞浸潤が少ない腫瘍に対しても併用療法が有効であり、新たな併用療法の１つとなる可能性が示唆された。