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. 2019 Feb 20;8(2):263.
doi: 10.3390/jcm8020263.

A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma

Ryogo Kikuchi  1   2 , Ryo Ueda  3   4 , Katsuya Saito  5 , Shunsuke Shibao  6 , Hideaki Nagashima  7 , Ryota Tamura  8 , Yukina Morimoto  9 , Hikaru Sasaki  10 , Shinobu Noji  11 , Yutaka Kawakami  12 , Kazunari Yoshida  13 , Masahiro Toda  14
Affiliations

A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma

Ryogo Kikuchi et al. J Clin Med. .

Abstract

High-grade gliomas (HGGs) carry a dismal prognosis despite current treatments. We previously confirmed the safety and immunogenicity of a vaccine treatment targeting tumor angiogenesis with synthetic peptides, for vascular endothelial growth factor receptor (VEGFR) epitopes in recurrent HGG patients. In this study, we evaluated a novel vaccine therapy targeting not only tumor vasculature but also tumor cells, using multiple glioma oncoantigen (GOA)/glioma angiogenesis-associated antigen (GAAA) peptides in HLA-A2402+ recurrent/progressive HGG patients. The vaccine included peptide epitopes from four GOAs (LY6K, DEPDC1, KIF20A, and FOXM1) and two GAAAs (VEGFR1 and VEGFR2). Ten patients received subcutaneous vaccinations. The primary endpoint was the safety of the treatment. T-lymphocyte responses against GOA/GAAA epitopes and treatment response were evaluated secondarily. The treatment was well tolerated without any severe systemic adverse events. The vaccinations induced immunoreactivity to at least three vaccine-targeted GOA/GAAA in all six evaluable patients. The median overall survival time in all patients was 9.2 months. Five achieved progression-free status lasting at least six months. Two recurrent glioblastoma patients demonstrated stable disease. One patient with anaplastic oligoastrocytoma achieved complete response nine months after the vaccination. Taken together, this regimen was well tolerated and induced robust GOA/GAAA-specific T-lymphocyte responses in recurrent/progressive HGG patients.

Keywords: high-grade glioma; oncoantigen; tumor angiogenesis; tumor associate antigen; vaccine therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival analysis of patients by the Kaplan–Meier method. (a) Overall survival (OS) curve of all patients (n = 10). The median OS time (mOS) of all patients was 9.2 months and 1-year OS was 44.4%; (b) OS curve of glioblastoma (GB) patients (n = 7). The mOS was 9.1 months and 1-year OS was 33.3% in GB patients.
Figure 1
Figure 1
Survival analysis of patients by the Kaplan–Meier method. (a) Overall survival (OS) curve of all patients (n = 10). The median OS time (mOS) of all patients was 9.2 months and 1-year OS was 44.4%; (b) OS curve of glioblastoma (GB) patients (n = 7). The mOS was 9.1 months and 1-year OS was 33.3% in GB patients.
Figure 2
Figure 2
Contrast-enhanced magnetic resonance images of Patient 6. (a) Tumor had recurred in a functional area; (b) tumor was decreased 3 months after enrollment; (c) tumor disappeared 9 months after enrollment.
Figure 3
Figure 3
Overall survival of glioblastoma patients with or without bevacizumab. The median overall survival time (mOS) was 23.6 months in three patients that did not receive bevacizumab before enrollment (solid line). The mOS was 8.6 months in four patients treated with bevacizumab before enrollment (dotted line).
See this image and copyright information in PMC

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