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

// Shunsuke Shibao 1 , Ryo Ueda 2 , Katsuya Saito 3 , Ryogo Kikuchi 1 , Hideaki Nagashima 1 , Atsuhiro Kojima 4 , Hiroshi Kagami 5 , Eriel Sandika Pareira 1 , Hikaru Sasaki 1 , Shinobu Noji 6 , Yutaka Kawakami 6 , Kazunari Yoshida 1 and Masahiro Toda 1 1 Department of Neurosurgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan 2 Department of Neurosurgery, Kawasaki Municipal Hospital, Kawasaki, Kawasaki-ku, Kawasaki, Kanagawa 210-0013, Japan 3 Department of Neurosurgery, Ashikaga Red Cross Hospital, Ashikaga, Tochigi 326-0843, Japan 4 Department of Neurosurgery, Saitama Municipal Hospital, Midori-ku, Saitama, Saitama 336-8522, Japan 5 Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Tsurumi-ku, Yokohama, Kanagawa 230-8765, Japan 6 Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan Correspondence to: Masahiro Toda, email: todam@keio.jp Keywords: high grade glioma; peptide vaccine; vascular endothelial growth factor receptor Received: August 08, 2017     Accepted: March 13, 2018     Published: April 20, 2018 ABSTRACT Object: 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. Methods: 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. Results: 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. Conclusion: These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.