Toh Uhi, Saku Shuko, Okabe Mina, Iwakuma Nobutaka, Kimitsuki Yuko, Akashi Momoko, Ogo Etsuyo, Yamada Akira, Shichijo Shigeki, Itoh Kyogo, Akagi Yoshito
Dept. of Surgery Kurume University School of Medicine.
Gan To Kagaku Ryoho. 2016 Oct;43(10):1249-1251.
Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC. All patients had histologically confirmed measurable ER-PgR-HER2- mBC and their human leukocyte antigen(HLA) / -A molecules were A2, A3, A11, A24, A26, A31, or A33. KRM-19(19mg/mL)was administrated subcutaneously every week for a total of 6 doses. Concurrent conventional chemo- and/or endocrine therapy were not permitted during treatment. This was an open-label, early phase II study. The primary endpoint was safety and anti-tumor immunologic effect, while the secondary endpoints were clinical responses and progression-free survival(PFS). The estimated enrollment was 10-15 and 8 patients were enrolled(Clinical trial registry number: UMIN000014616). Measurement of peptide-specific cytotoxic T lymphocyte and IgG responses were conducted before and after vaccination. The correlation between PFS and the increased IgG response and/or CTL levels were investigated.
我们之前的II期临床试验表明，经治疗选择的个性化肽疫苗（PPV）在增强抗癌免疫力方面是有效的；PPV后的免疫反应与作为转移性乳腺癌（mBC）预后因素的临床结果相关。我们进行了一项早期II期研究，以评估一种使用多种肽疫苗（KRM-19）的新方案对转移性三阴性乳腺癌患者的安全性和疗效。KRM-19由根据其对mBC患者的抗肿瘤免疫效应和安全性概况从先前报道的31种PPV中选择的19种混合肽组成。所有患者均经组织学证实为可测量的ER-PgR-HER2- mBC，且其人类白细胞抗原（HLA）/-A分子为A2、A3、A11、A24、A26、A31或A33。KRM-19（19mg/mL）每周皮下注射一次，共6剂。治疗期间不允许同时进行传统的化疗和/或内分泌治疗。这是一项开放标签的早期II期研究。主要终点是安全性和抗肿瘤免疫效应，次要终点是临床反应和无进展生存期（PFS）。估计入组人数为10-15人，共有8名患者入组（临床试验注册号：UMIN-CTR000014616）。在接种疫苗前后进行肽特异性细胞毒性T淋巴细胞和IgG反应的检测。研究了PFS与IgG反应增加和/或CTL水平之间的相关性。
