Miyazawa Motoki, Yamaue Hiroki
Second Dept. of Surgery, Wakayama Medical University.
Gan To Kagaku Ryoho. 2011 Nov;38(12):1903-5.
Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and the growth of pancreatic cancer. In addition, it is overexpressed in tumor blood vessels, however, VEGFR2 is not expressed in normal vessels, which makes an attractive candidate as a molecular target for antiangiogenic cancer immunotherapy. Furthermore, the tumor cell-indirect immunotherapy targeting VEGFR2 is expected to overcome tumor immune escape. The phase I clinical trial using VEGFR2-169 peptide that successfully induced specific CTLs in cancer patients, combined with gemcitabine (GEM), was conducted for patients with advanced pancreatic cancer. VEGFR2-169 was subcutaneously injected weekly in a dose-escalation manner( doses of 0.5, 1.0, 2.0 mg/body, 6 patients/1 cohort). GEM was administered at a dose of 1,000 mg/m2 on days 1, 8 and 15 in a 28-day cycle. No dose limiting toxicity was observed. Specific CTLs reacting to VEGFR2-169 were induced in 11 (61%) of the 18 patients. Our protocol was safe and well-tolerated. VEGFR2-169 was immunogenic under the condition with GEM treatment. From an immunological point of view, the optimal dose might be 2.0 mg/body. A randomized phase II/III clinical trial started in January 2009 to demonstrate the clinical benefits of VEGFR2-169 for advanced pancreatic cancer patients.
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关键因子。此外，它在肿瘤血管中过度表达，然而，VEGFR2在正常血管中不表达，这使其成为抗血管生成癌症免疫治疗的有吸引力的分子靶点。此外，靶向VEGFR2的肿瘤细胞间接免疫疗法有望克服肿瘤免疫逃逸。对晚期胰腺癌患者进行了使用VEGFR2 - 169肽的I期临床试验，该肽成功诱导癌症患者产生特异性细胞毒性T淋巴细胞（CTL），并联合吉西他滨（GEM）。以剂量递增方式（剂量为0.5、1.0、2.0mg/体，每组6例患者）每周皮下注射VEGFR2 - 169。在28天周期的第1、8和15天，以1000mg/m²的剂量给予GEM。未观察到剂量限制性毒性。18例患者中有11例（61%）诱导出对VEGFR2 - 169有反应的特异性CTL。我们的方案安全且耐受性良好。在GEM治疗条件下，VEGFR2 - 169具有免疫原性。从免疫学角度来看，最佳剂量可能是2.0mg/体。一项随机II/III期临床试验于2009年1月开始，以证明VEGFR2 - 169对晚期胰腺癌患者的临床益处。
