Malignant astrocytomas are among the most common and deadly brain tumors of childhood. Most children with brainstem and subtotally resected non-brainstem malignant gliomas die within several years of diagnosis, despite current treatments. Accordingly, new treatment approaches are needed that target the unique features of these tumors. During the last decade, we have gained significant preclinical and clinical experience with immunotherapy for adult gliomas, and propose to extend these insights to the treatment of childhood malignant gliomas, based on our observation of substantial similarities between these tumors in their expression of glioma-associated antigens (GAAs). Building upon these data, we propose the use of a GAA- based vaccine cocktail, combined with an immunoadjuvant (poly-ICLC), for children with newly diagnosed malignant brainstem gliomas (Stratum 1) and subtotally resected non-brainstem malignant gliomas (Stratum 2). Participants will be treated with s.c. injections of GAA vaccines every 3 weeks for 8 courses and poly-ICLC will be administered (30 Our clinical study and biological correlative analyses will represent the first application of a multipeptide epitope vaccine-based strategy to a pediatric glioma cohort, providing fundamental data for assessing safety, and clinical and immunological efficacy, of immunotherapeutic strategies in the pediatric brain tumor context.Public Health Relevance
