Immunotherapy for malignant glioma.
Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Carter M
CM
Suryadevara
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Terence
T
Verla
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Luis
L
Sanchez-Perez
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Elizabeth A
EA
Reap
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Bryan D
BD
Choi
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Peter E
PE
Fecci
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
John H
JH
Sampson
Adoptive cell transfer; brain tumors; central nervous system; glioma; immunotherapy