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

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...

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Autores principales: Kikuchi, Ryogo, Ueda, Ryo, Saito, Katsuya, Shibao, Shunsuke, Nagashima, Hideaki, Tamura, Ryota, Morimoto, Yukina, Sasaki, Hikaru, Noji, Shinobu, Kawakami, Yutaka, Yoshida, Kazunari, Toda, Masahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406695/
https://www.ncbi.nlm.nih.gov/pubmed/30791546
http://dx.doi.org/10.3390/jcm8020263
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author Kikuchi, Ryogo
Ueda, Ryo
Saito, Katsuya
Shibao, Shunsuke
Nagashima, Hideaki
Tamura, Ryota
Morimoto, Yukina
Sasaki, Hikaru
Noji, Shinobu
Kawakami, Yutaka
Yoshida, Kazunari
Toda, Masahiro
author_facet Kikuchi, Ryogo
Ueda, Ryo
Saito, Katsuya
Shibao, Shunsuke
Nagashima, Hideaki
Tamura, Ryota
Morimoto, Yukina
Sasaki, Hikaru
Noji, Shinobu
Kawakami, Yutaka
Yoshida, Kazunari
Toda, Masahiro
author_sort Kikuchi, Ryogo
collection PubMed
description 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.
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spelling pubmed-64066952019-03-22 A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma Kikuchi, Ryogo Ueda, Ryo Saito, Katsuya Shibao, Shunsuke Nagashima, Hideaki Tamura, Ryota Morimoto, Yukina Sasaki, Hikaru Noji, Shinobu Kawakami, Yutaka Yoshida, Kazunari Toda, Masahiro J Clin Med Article 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. MDPI 2019-02-20 /pmc/articles/PMC6406695/ /pubmed/30791546 http://dx.doi.org/10.3390/jcm8020263 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kikuchi, Ryogo
Ueda, Ryo
Saito, Katsuya
Shibao, Shunsuke
Nagashima, Hideaki
Tamura, Ryota
Morimoto, Yukina
Sasaki, Hikaru
Noji, Shinobu
Kawakami, Yutaka
Yoshida, Kazunari
Toda, Masahiro
A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title_full A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title_fullStr A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title_full_unstemmed A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title_short A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
title_sort pilot study of vaccine therapy with multiple glioma oncoantigen/glioma angiogenesis-associated antigen peptides for patients with recurrent/progressive high-grade glioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406695/
https://www.ncbi.nlm.nih.gov/pubmed/30791546
http://dx.doi.org/10.3390/jcm8020263
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