Abstract
Recurrent medulloblastoma and malignant glioma are lethal tumors that are virtually incurable. The cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed on medulloblastoma and malignant glioma but not on healthy brain, making this an attractive candidate for targeted therapy, including immunotherapy. A recently completed phase I trial at Duke evaluated autologous CMV pp65 RNA-pulsed dendritic cell (DC) vaccines in newly diagnosed adult glioblastoma patients. Vaccines were most effective when given with GM-CSF after tetanus-diphtheria toxoid (Td) site preconditioning, achieving a median overall survival of over 40 months. Additionally, DC migration to lymph nodes emerged as a strong biologic correlate with progression-free survival. We are now evaluating this platform in children as a single-arm phase I trial. Our hypothesis is that pp65 RNA-pulsed autologous DC vaccines will be well-tolerated and lead to significant DC migration and pp65-specific T cell responses in children with recurrent medulloblastoma or malignant glioma. As the primary objective, we will establish the safety and feasibility of vaccinating pediatric patients with recurrent medulloblastoma or malignant glioma using CMV pp65 RNA-pulsed DCs with GM-CSF and Td preconditioning. Our secondary objectives are to 1.) assess the ability of radiolabeled DCs to track to vaccine-draining lymph nodes, and 2.) measure T-cell responses against pp65 before and after DC vaccination. Time to progression is not a primary endpoint in this study but will be accessioned to derive hypotheses that may relate other data derived in this study with progression.
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