Oncotarget

Clinical Research Papers:

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

Shunsuke Shibao, Ryo Ueda, Katsuya Saito, Ryogo Kikuchi, Hideaki Nagashima, Atsuhiro Kojima, Hiroshi Kagami, Eriel Sandika Pareira, Hikaru Sasaki, Shinobu Noji, Yutaka Kawakami, Kazunari Yoshida and Masahiro Toda _

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Oncotarget. 2018; 9:21569-21579. https://doi.org/10.18632/oncotarget.25131

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Abstract

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

Correspondence to:

Masahiro Toda, email: [email protected]

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.


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