Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer
Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer
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DOI：
10.1111/j.1349-7006.2009.01416.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
--
作者：
Miyazawa, Motoki;Ohsawa, Ryuji;Yamaue, Hiroki
血管内皮生长因子受体 2 (VEGFR2) 是肿瘤血管生成和胰腺癌生长的重要因子。使用我们之前确定的 VEGFR2 (VEGFR2-169) 表位肽的免疫疗法预计将改善临床结果。因此，针对晚期胰腺癌患者开展了VEGFR2-169联合吉西他滨的I期临床试验。患有转移性和不可切除的胰腺癌的患者有资格参加该试验。吉西他滨在 28 天周期的第 1、8 和 15 天以 1000 mg/m(2) 的剂量给药。每周以剂量递增的方式皮下注射 VEGFR2-169 肽（剂量为 0.5、1 和 2 mg/体，六名患者/一组）。评估安全性和免疫学参数。未观察到 4 级或以上的严重不良反应。在完成至少一个疗程的 18 名患者中，15 名（83%）在注射部位出现了免疫反应。 18 名患者中有 11 名 (61%) 诱导了与 VEGFR2-169 肽发生反应的特异性细胞毒性 T 淋巴细胞 (CTL)。疾病控制率为67%，中位总生存时间为8.7个月。这种对胰腺癌患者的联合疗法在所有剂量下都是可以耐受的。即使与吉西他滨联合使用，VEGFR2-169 肽疫苗也可以高效率诱导肽特异性 CTL。从免疫学角度来看，进一步临床试验的最佳剂量可能是2 mg/体或更高。该试验已在 ClinicalTrial.gov 注册（编号 NCT 00622622）。 （癌症科学 2010 年；101：433-439）
Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2-169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2-169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m(2) on days 1, 8, and 15 in a 28-day cycle. The VEGFR2-169 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2-169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide-specific CTL could be induced by the VEGFR2-169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 00622622). (Cancer Sci 2010; 101: 433-439)