Development of a new immunotherapy activating both cytotoxic and helper T cells against bladder cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293353
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyushu University (2015-2016); 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): 河野 吉昭 熊本大学, その他の研究科, 講師 (30593793)
• Co-Investigator(Renkei-kenkyūsha): NISHIMURA Yasuharu 熊本大学, 大学院生命科学研究部, 教授 (10156119)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 癌 / 免疫学 / トランスレーショナルリサーチ

Outline of Final Research Achievements

In this study, we have succeeded in identifying 4 long peptides (LPs) that comprise from 22-29 amino acids originated from Bladder cancer tumor-associated antigens (TAA). We confirmed the immunogenecity of LPs from Bladder cancer TAA (TAA-LP) by induction of TAA-LP-specific helper T (Th) cells from healthy donors. We could also detect type 1 Th (Th1) cells specific for TAA-LPs from Bladder cancer patients. Using transgenic mice expressing human HLA-A2, we next showed the induction of cytotoxic T cells (CTLs) specific for short peptides (SPs) from Bladder cancer TAA (TAA-SP), even after immunization with TAA-LPs, indicating the cross-presentation to Th cells and CTLs by TAA-LPs. We also succeeded in the enhancemant of CTLs against TAA-SPs when combined with LPs, Th clones, and anti-PD-1 mAb, implicating the new strategy of combination therapy with TAA-LPs. The above results have indicated that TAA-LPs are effective, and can be a new treatment option for patients with Bladder cancer.

Free Research Field

泌尿器腫瘍学