Obara Wataru, Sato Fuminori, Takeda Kazuyoshi, Kato Renpei, Kato Yoichiro, Kanehira Mitsugu, Takata Ryo, Mimata Hiromitsu, Sugai Tamotsu, Nakamura Yusuke, Fujioka Tomoaki
Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan.
Department of Urology, Oita University Faculty of Medicine, Oita, Japan.
Cancer Sci. 2017 Jul;108(7):1452-1457. doi: 10.1111/cas.13278. Epub 2017 Jun 23.
Cell division associated 1 (CDCA1) was screened as an oncogene that is overexpressed on several cancers, including prostate cancer. A highly immunogenic HLA-A2402-restricted epitope peptide corresponding to part of the CDCA1 protein was also identified. A phase I clinical trial was conducted for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1.0 or 3.0 mg/body, six patients received each dose). The primary endpoint was safety, and the secondary endpoints were the immunological and clinical responses. Vaccination with CDCA1 peptide was well tolerated without any serious adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses using ELISPOT assay and dextramer assay were observed in three patients receiving the 1.0 mg dose and five patients receiving the 3.0 mg dose. The median overall survival time was 11.0 months and specific CTL reacting to CDCA1 peptide were recognized in long-surviving patients. CDCA1-derived peptide vaccine treatment was tolerable and might effectively induce peptide-specific CTLs for CRPC patients. This novel peptide vaccine therapy for CRPC appears promising. (ClinicalTrials.gov number, NCT01225471).
细胞分裂相关蛋白1（CDCA1）被筛选为一种在包括前列腺癌在内的多种癌症中过度表达的癌基因。还鉴定出一种与CDCA1蛋白部分相对应的高免疫原性HLA - A2402限制性表位肽。对去势抵抗性前列腺癌（CRPC）患者进行了一项使用CDCA1肽疫苗的I期临床试验。招募了12例多西他赛化疗失败后患有CRPC且HLA - A2402阳性的患者。他们以剂量递增的方式（剂量为1.0或3.0mg/体，各有6例患者接受该剂量）每周一次皮下注射与Montanide ISA51VG乳化的CDCA1肽。主要终点是安全性，次要终点是免疫和临床反应。CDCA1肽疫苗接种耐受性良好，未发生任何严重不良事件。在接受1.0mg剂量的3例患者和接受3.0mg剂量的5例患者中观察到使用ELISPOT测定法和dextramer测定法的肽特异性细胞毒性T淋巴细胞（CTL）反应。中位总生存时间为11.0个月，在长期存活患者中识别出对CDCA1肽有反应的特异性CTL。CDCA1衍生肽疫苗治疗耐受性良好，可能有效诱导CRPC患者产生肽特异性CTL。这种针对CRPC的新型肽疫苗疗法似乎很有前景。（ClinicalTrials.gov编号，NCT01225471）
