Cancer Immunol Immunother
Obara, Wataru Iwate Medical University
Karashima, Takashi Kochi Medical School
Takeda, Kazuyoshi Juntendo University
Kato, Renpei Iwate Medical University
Kato, Yoichiro Iwate Medical University
Kanehira, Mitsugu Iwate Medical University
Takata, Ryo Iwate Medical University
Inoue, Keiji Kochi Medical School
Katagiri, Toyomasa Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Shuin, Taro Kochi Medical School
Nakamura, Yusuke The University of Chicago
Fujioka, Tomoaki Iwate Medical University
Cancer peptide vaccine
Genome-wide expression profile
Cytotoxic T lymphocyte
Renal cell carcinoma
Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC.
Materials and Methods
Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses.
Vaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months.
HIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising.
Cancer Immunology, Immunotherapy
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Institute of Advanced Medical Sciences