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, Masahiro Toda

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)21569-21579
Number of pages11
JournalOncotarget
Volume9
Issue number30
DOIs
Publication statusPublished - 2018 Apr 20

Fingerprint

Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Subunit Vaccines
Glioma
Vascular Endothelial Growth Factor Receptor
Epitopes
Vaccination
Vaccines
Safety
Cancer Vaccines
Survival
Angiogenesis Inducing Agents
Interleukin-8
Blood Cells
Neoplasms
Enzyme-Linked Immunosorbent Assay
T-Lymphocytes
Peptides

Keywords

  • High grade glioma
  • Peptide vaccine
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Oncology

Cite this

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

In: Oncotarget, Vol. 9, No. 30, 20.04.2018, p. 21569-21579.

Research output: Contribution to journalArticle

Shibao, S, Ueda, R, Saito, K, Kikuchi, R, Nagashima, H, Kojima, A, Kagami, H, Pareira, ES, Sasaki, H, Noji, S, Kawakami, Y, Yoshida, K & Toda, M 2018, 'A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma', Oncotarget, vol. 9, no. 30, pp. 21569-21579. https://doi.org/10.18632/oncotarget.25131
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. / A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma. In: Oncotarget. 2018 ; Vol. 9, No. 30. pp. 21569-21579.
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