HG-86IMMUNOTHERAPY OF WILMS TUMOR 1 PEPTIDE VACCINATION AGAINST RECURRENT GLIOBLASTOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA IN CHILDREN

Abstract

Background: We have ever proven safety and effectiveness of Wilms tumor 1 peptide (WT1) vaccination for newly-diagnosed or recurrent glioblastomas (GBM) in adult. But pediatric GBM and diffuse intrinsic pontine glioma (DIPG) are known to differ from adult GBM biologically. A pilot study designed to investigate safety and effectiveness of Wilms tumor 1 peptide vaccination for recurrent GBM and DIPG in children was planned. PATIENTS AND Methods: HLA-A∗2402-positive five children with recurrent malignant glioma (three GBMs and two DIPGs) were registered in this clinical study ofWT1immunotherapy. In all children, the tumors were resistant to standard therapy including radiation and temozolomide. Patients received intradermal injections of an HLA-A∗2402-restricted, WT1 peptide every week for 12 weeks. Patients with an effective response continued to be vaccinated until tumor progression occurred or performance status deteriorated. Progression-free survival and overall survival after initial WT1 treatment were analysed. Results: In all patients, no severe adverse event was observed. The protocol was well tolerated in children. The 6-month progressionfree survival rate was 60%. Progression-free survival and overall survival were significantly improved as compared with historical control in Osaka University Hospital. Two patients with supratentorial GBM are still alive more than three years. Conclusions: This study showed that WT1 vaccine therapy against recurrent GBM and DIPG in HLA-A∗2402-positive children was safe and improved their prognosis. Based on these Results, further clinical studies of WT1 immunotherapy in children suffering from newly diagnosed or recurrent malignant glioma should be authorized.