[The development of a novel cancer vaccine using Peptide vaccine for patients with advanced pancreatic cancer].

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.