DUANE MITCHELL, M.D., Ph.D.
Duke University Medical Center

“RNA Loaded Dendritic Cell Vaccines Targeting Brain Tumor Stem Cells During Hematopoietic Recovery from Temozolomide-induced Lymphopenia”

Our mission is to develop safe and effective immunotherapies for the treatment of malignant brain tumors. Past clinical trials at Duke using vaccination directed against a brain tumor specific mutation (EGFRvIII) have shown great potential, including significant immunologic responses in treated patients, near complete radiographic remissions of all residual tumors, and encouraging prolongation of survival in patients with glioblastoma (GBM).

Currently, Duke’s clinical investigations have not shown any adverse effects of immunotherapy in treated patients. These encouraging results have prompted the initiation of a Phase III clinical vaccine trial targeting the EGFRvIII mutation. This mutation however, is not present in the majority of malignant brain tumors, so more widely applicable approaches are still needed.

Recent studies have identified a population of tumor cells called “brain tumor stem cells” that are more resistant to standard radiation and chemotherapy and may be the cause of tumor recurrence. The goal of Dr. Mitchell’s study is to test immunotherapy directed specifically against these brain tumor stem cells. It is hoped that this may be especially effective at eliminating residual tumor, and this proposal aims to evaluate the safety and effectiveness of vaccination directed at antigens present within brain tumor stem cells.

There exists the capacity to amplify the genetic content from small numbers of brain tumor stem cells isolated from surgically resected tumors and generate sufficient material for clinical vaccination directed against these cells. In this study, Dr. Mitchell and his team will investigate the use of the most powerful stimulatory cells of the immune system, called dendritic cells, to enhance immunologic responses directed against brain tumor stem cells.

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