Clinical evaluation of efficacy and safety of dendritic cell-based vaccine therapy using with HLA-A2 restricted IL-13 alpha receptor peptide in patients with malignant glioma managed by international organization for standardization

针对树突状细胞特异性抗原肽治疗恶性脑肿瘤，2006年开始临床前研究评估，2007年开始临床试验。在名古屋大学附属医院遗传与再生医学中心（CGRM）的支持下，获得了ISO（国际标准化组织）9001:2000和13485:2003认证。这是日本第一家获得ISO质量认证的学术机构。在此基础上，它计划与日本工业和学术中心的客户合作，在工艺开发和验证以及GMP/GTP（良好组织规范）生产方面提供帮助。在那里，它负责各种新型细胞的工艺开发、验证和GMP（良好生产规范）生产，包括树突状细胞疫苗、抗原特异性ctl（细胞毒性T淋巴细胞）。为了改善恶性胶质瘤的预后，最近出现了免疫IL13R α 2肽的树突状细胞治疗，据报道，IL13R α 2肽在胶质瘤中丰富且特异性过表达。人白细胞抗原(BLA) -A2阳性的组织学证实的恶性胶质瘤患者被纳入研究。外周血单核细胞积累后，Clini MACS收集CD14阳性细胞。与细胞因子（IL-4和GM-CSF）孵育一周后，成熟的dc以IL13R α 2肽脉冲，患者以2周间隔皮内接种4次。虽然有少量临床试验（4例），但这种DC治疗已显示出安全性；治疗期间患者病情稳定。本研究提示树突状细胞免疫IL13R α 2肽进行临床试验的可行性和安全性，可能成为恶性胶质瘤患者新的治疗选择。

As for dendritic cell therapy for malignant brain tumor using with specified antigen peptide, pre-clinical research had been evaluated until 2006 Since 2007, Clinical trial has started. with the support of the center for Genetic and Regenerative Medicine (CGRM) in our Hospital, which is an institute to put advanced medicine into practice in Nagoya University Hospital, gained ISO (International Organization for Standardization)9001 : 2000 and 13485 : 2003 Accreditation. It is the first academic institute in Japan to achieve the ISO Quality. Under this, it has been planed to work with clients in industry and academic centers in Japan, providing assistance in process development and validation, and GMP/GTP (Good Tissue Practice) production. There it has been responsible for process development, validation, and GMP (Good Manufacturing Practice) production of a broad range of novel cell including dendritic cell vaccines, antigen-specific CTLs (cytotoxic T lymphocytes).In order to improve the prognosis of malignant glioma, dendritic cell therapy vaccinated with IL13R alpha 2 peptide, which reported to be abundantly and specifically overexpressed in glioma, has recently emerged. Patients positive for human leukocyte antigen (BLA) -A2 with histologically confirmed malignant glioma were enrolled. After accumulation of peripheral blood monocyte, CD14 positive cells were collected by Clini MACS. After one week incubation with cytokines (IL-4 and GM-CSF), matured DCs were pulsed by IL13R alpha 2 peptide, and patients were inoculated intradermally four times at 2-week intervals. Although there is small number of clinical trial (four patients), this DC therapy has shown safety; and patients were stable during treatment period. This study suggests the feasibility and safety of dendritic cell therapy vaccinated with IL13R alpha 2 peptide for clinical trial, which may become a new treatment options for patients with malignant gliomas.