A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma

• Published in: Oncotarget 2018-04, Vol.9 (30), p.21569-21579
• Main Authors: Shibao, Shunsuke, Ueda, Ryo, Saito, Katsuya, Kikuchi, Ryogo, Nagashima, Hideaki, Kojima, Atsuhiro, Kagami, Hiroshi, Pareira, Eriel Sandika, Sasaki, Hikaru, Noji, Shinobu, Kawakami, Yutaka, Yoshida, Kazunari, Toda, Masahiro
• Format: Article
• Language: English
• Subjects: Clinical Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.25131

Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.