Clinical Research Papers:
A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma
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Shunsuke Shibao1, Ryo Ueda2, Katsuya Saito3, Ryogo Kikuchi1, Hideaki Nagashima1, Atsuhiro Kojima4, Hiroshi Kagami5, Eriel Sandika Pareira1, Hikaru Sasaki1, Shinobu Noji6, Yutaka Kawakami6, Kazunari Yoshida1 and Masahiro Toda1
1Department of Neurosurgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
2Department of Neurosurgery, Kawasaki Municipal Hospital, Kawasaki, Kawasaki-ku, Kawasaki, Kanagawa 210-0013, Japan
3Department of Neurosurgery, Ashikaga Red Cross Hospital, Ashikaga, Tochigi 326-0843, Japan
4Department of Neurosurgery, Saitama Municipal Hospital, Midori-ku, Saitama, Saitama 336-8522, Japan
5Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Tsurumi-ku, Yokohama, Kanagawa 230-8765, Japan
6Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
Masahiro Toda, email: firstname.lastname@example.org
Keywords: high grade glioma; peptide vaccine; vascular endothelial growth factor receptor
Received: August 08, 2017 Accepted: March 13, 2018 Published: April 20, 2018
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.
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