Asahara Shingo, Takeda Kazuyoshi, Yamao Kenji, Maguchi Hiroyuki, Yamaue Hiroki
Department of Internal Medicine, Chiba Tokushukai Hospital, Chiba, Japan.
J Transl Med. 2013 Nov 16;11:291. doi: 10.1186/1479-5876-11-291.
We previously developed an immunotherapy treatment utilizing a cancer vaccine reagent KIF20A-66 in order to treat pancreatic cancer. KIF20A-66 is HLA-A24-restricted epitope peptide derived from KIF20A, a member of kinesin super family protein 20A that is significantly transactivated in pancreatic cancer. In this report, we further demonstrated non-randomized, open-label, single centered phase I/II clinical trial of immunotherapy using the KIF20A-66 peptide for the patients with advanced pancreatic cancer.
Vaccination was performed to the patients with metastatic pancreatic cancer, in whom gemcitabine-based therapy had failed. In phase I study, KIF20A-66 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 1.0 and 3.0 mg/body, 6 patients/1 cohort). After safety was assessed, phase II study was conducted using 3.0 mg of KIF20A-66 peptide.
KIF20A-66 peptide vaccination was well tolerated in the doses we examined and tumor responses after 1 month of the treatment were evaluated. Among 29 patients who completed one course of the treatment at least, stable disease (SD) was found in 21 cases, while progressive disease (PD) was found in 8 cases, indicating that the disease control rate was 72%. Objective tumor shrinkage was observed in 8 cases, including 1 case of complete response (CR). The median survival time (MST) and progression free survival time (PFS) were 142 days and 56 days, respectively. These results clearly demonstrate that overall survival of the patients was significantly prolonged, compared to the historical controls of 9 cases with unmatched HLA in the same hospital (MST: 83 days), as well as 81 cases in our and other hospitals (MST: 63 days).
The patients vaccinated with KIF20A-66 peptide had better prognosis than the control group with best supportive care (BSC). Thus, we concluded that KIF20A-66 vaccination is significantly effective as an immunotherapy against advanced pancreatic cancer. KIF20A-66 peptide was well tolerable in the dose of either 1.0 mg or 3.0 mg/body, and effectively induced peptide-specific response of cytotoxic T lymphocyte (CTL). Further clinical study using this peptide is a promising approach for advanced pancreatic cancer to achieve high potential benefit for better prognosis.
UMIN-CTR, number UMIN000004919.
我们之前研发了一种利用癌症疫苗试剂KIF20A - 66的免疫疗法来治疗胰腺癌。KIF20A - 66是一种源自KIF20A的HLA - A24限制性表位肽，KIF20A是驱动蛋白超家族蛋白20A的成员，在胰腺癌中显著反式激活。在本报告中，我们进一步展示了使用KIF20A - 66肽对晚期胰腺癌患者进行免疫疗法的非随机、开放标签、单中心I/II期临床试验。
对吉西他滨为基础的治疗失败的转移性胰腺癌患者进行疫苗接种。在I期研究中，以剂量递增方式（剂量为1.0和3.0mg/体，每组6例患者）每周皮下注射KIF20A - 66肽。在评估安全性后，使用3.0mg的KIF20A - 66肽进行II期研究。
在我们检测的剂量下，KIF20A - 66肽疫苗接种耐受性良好，并评估了治疗1个月后的肿瘤反应。在至少完成一个疗程治疗的29例患者中，21例出现疾病稳定（SD），8例出现疾病进展（PD），疾病控制率为72%。观察到8例患者肿瘤出现客观缩小，其中1例完全缓解（CR）。中位生存时间（MST）和无进展生存时间（PFS）分别为142天和56天。这些结果清楚地表明，与同一医院9例不匹配HLA的历史对照患者（MST：83天）以及我们医院和其他医院的81例患者（MST：63天）相比，患者的总生存期显著延长。
接种KIF20A - 66肽的患者比接受最佳支持治疗（BSC）的对照组预后更好。因此，我们得出结论，KIF20A - 66疫苗接种作为晚期胰腺癌的免疫疗法具有显著疗效。KIF20A - 66肽在剂量为1.0mg或3.0mg/体时耐受性良好，并有效诱导细胞毒性T淋巴细胞（CTL）的肽特异性反应。使用该肽的进一步临床研究是晚期胰腺癌实现更好预后高潜在获益的有前景的方法。
UMIN - CTR，编号UMIN000004919。
