Cancer Peptide Vaccine Therapy Developed from Oncoantigens Identified through Genome-wide Expression Profile Analysis for Bladder Cancer

被引:63
作者
Obara, Wataru [1 ]
Ohsawa, Ryuji [2 ,3 ]
Kanehira, Mitsugu [1 ]
Takata, Ryo [1 ]
Tsunoda, Takuya [2 ]
Yoshida, Koji [2 ]
Takeda, Kazuyoshi [4 ]
Katagiri, Toyomasa [2 ,5 ]
Nakamura, Yusuke [2 ]
Fujioka, Tomoaki [1 ]
机构
[1] Iwate Med Univ, Sch Med, Dept Urol, Morioka, Iwate 0208505, Japan
[2] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genome, Tokyo, Japan
[3] Wakayama Med Univ, Dept Surg 2, Wakayama, Japan
[4] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
[5] Univ Tokushima, Div Genome Med, Tokushima, Japan
关键词
cancer peptide vaccine; oncoantigen; genome-wide expression profile; bladder cancer; CELL VACCINATION; T-CELLS; IMMUNOTHERAPY; TRIAL; RESPONSES; SURVIVAL; TARGET; CHEMOTHERAPY; METHOTREXATE; GEMCITABINE;
D O I
10.1093/jjco/hys069
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis. Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer. We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo. The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.
引用
收藏
页码:591 / 600
页数:10
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