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

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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.