Adoptive cellular therapy after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has previously been limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority of other cancers. We demonstrate that tumor RNA-pulsed dendritic cells can be used to reliably expand CD4+ and CD8+ tumor-reactive T lymphocytes for curative adoptive cellular therapy in a highly-invasive, chemotherapy- and radiation-resistant malignant glioma model. Curative treatment of established intracranial tumors involved a synergistic interaction between myeloablative conditioning and hematopoietic stem cell transfer, adoptively transferred tumor-specific T cells, and tumor RNA-pulsed dendritic cell (DC) vaccines. By employing this platform we activate a polyclonal population of tumor reactive T cells and have further identified tumor-specific repertoires of tumor-reactive CD8+ T lymphocytes. Furthermore, we have observed a significant increase of clonotypic frequency of tumor-specific CD8+ cells by following TCR beta chain expression in mice that are cured of established tumor by adoptive cellular therapy, indicating the ability to potentially predict treatment outcomes in a preclinical setting. Clinical studies exploring the feasibility and potential survival benefit of this platform against both pediatric and adult CNS malignancies are currently underway in our institution. Our adoptive cellular therapy platform has demonstrated superior immunologic treatment of malignant gliomas and holds potential against other solid tumors.