A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
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DOI：
10.3390/jcm8020263
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发表时间：
2019-02-01
影响因子：
3.9
通讯作者：
Toda, Masahiro
中科院分区：
文献类型：
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作者：
Kikuchi, Ryogo;Ueda, Ryo;Toda, Masahiro
尽管目前的治疗方法，高级别胶质瘤（HGGs）的预后很差。我们之前证实了一种针对复发性HGG患者血管内皮生长因子受体（VEGFR）表位的合成肽靶向肿瘤血管生成的疫苗治疗的安全性和免疫原性。在这项研究中，我们在HLA-A2402阳性的复发/进展性HGG患者中，利用多发性胶质瘤癌抗原(GOA)/胶质瘤血管生成相关抗原（GAAA）肽，评估了一种不仅针对肿瘤血管系统，而且针对肿瘤细胞的新型疫苗治疗方法。该疫苗包含4个GOAs （LY6K、DEPDC1、KIF20A和FOXM1）和2个gaas （VEGFR1和VEGFR2）的肽表位。10例患者接受了皮下疫苗接种。主要终点是治疗的安全性。其次评价t淋巴细胞对GOA/GAAA表位的反应和治疗反应。治疗耐受性良好，无任何严重的全身不良事件。在所有6名可评估的患者中，接种疫苗诱导了对至少3种疫苗靶向GOA/GAAA的免疫反应性。所有患者的中位总生存期为9.2个月。5例患者的无进展状态持续至少6个月。2例复发性胶质母细胞瘤患者病情稳定。一名间变性少星形细胞瘤患者在接种疫苗9个月后获得完全缓解。综上所述，该方案耐受性良好，并在复发/进展性HGG患者中诱导了强大的GOA/ gaaa特异性t淋巴细胞反应。
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.