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

Abstract

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.

Immunotherapy of the Pancreatic Cancer

“…Peptidespecific 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 (74) .…”

Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes

“…39 To generate cancer vaccines, many different strategies have been evaluated in clinical trials, including adjuvant peptides, inactivated cancer cells, DNA, and even mRNA. 40,41 These vaccination strategies can elicit host immune responses, but these low-level responses often have limited efficacy. Although such treatment strategies have been shown to clearly stabilize disease, there have been very few examples of tumor regression.…”

Cancer vaccine therapy based on peptides

“…Based on the promising results of phase I trial using Elpamotide, a randomized phase II/ III trial was carried out for patients with advanced pancreatic cancer (PEGASUS-PC Study) [42,43] . Patients were randomly allocated to either Active group (Elpamotide + Gemcitabine) or Placebo group (Placebo + Gemcitabine) at 2:1 ratio.…”