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Gene Therapy for Brain Tumors
Christof M. Kramm,
Miguel Sena-Esteves,
Faith H. Barnett,
Nikolai G. Rainov,
Deborah E. Schuback,
John S. Yu,
Peter A. Pechan,
Werner Paulus,
E. Antonio Chiocca,
Xandra O. Breakefield,
Christof M. Kramm
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
University Children's Hospital, Heinrich-Heine-University, Duesseldorf, Germany
Search for more papers by this authorMiguel Sena-Esteves
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorFaith H. Barnett
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Children's Hospital/Brigham and Women's Hospital, Boston, MA, USA
Search for more papers by this authorNikolai G. Rainov
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Department of Neurosurgery, Martin-Luther-University, Halle (Saale), Germany
Search for more papers by this authorDeborah E. Schuback
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorJohn S. Yu
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Massachusetts General Hospital, Boston, MA, USA
Search for more papers by this authorPeter A. Pechan
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorWerner Paulus
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Institute of Neuropathology, Department of Pathology, University Hospital Zurich, Switzerland
Search for more papers by this authorE. Antonio Chiocca
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Massachusetts General Hospital, Boston, MA, USA
Search for more papers by this authorCorresponding Author
Xandra O. Breakefield
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Corresponding author: Dr. Xandra O. Breakefield, Massachusetts General Hospital East, Molecular Neurogenetics Unit, 13th St., Bldg. 149, Charlestown, MA 02129, USA Tel. +1 (617) 726–5728, Fax + 1 (617) 726–5736Search for more papers by this authorChristof M. Kramm,
Miguel Sena-Esteves,
Faith H. Barnett,
Nikolai G. Rainov,
Deborah E. Schuback,
John S. Yu,
Peter A. Pechan,
Werner Paulus,
E. Antonio Chiocca,
Xandra O. Breakefield,
Christof M. Kramm
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
University Children's Hospital, Heinrich-Heine-University, Duesseldorf, Germany
Search for more papers by this authorMiguel Sena-Esteves
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorFaith H. Barnett
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Children's Hospital/Brigham and Women's Hospital, Boston, MA, USA
Search for more papers by this authorNikolai G. Rainov
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Department of Neurosurgery, Martin-Luther-University, Halle (Saale), Germany
Search for more papers by this authorDeborah E. Schuback
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorJohn S. Yu
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Massachusetts General Hospital, Boston, MA, USA
Search for more papers by this authorPeter A. Pechan
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorWerner Paulus
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Institute of Neuropathology, Department of Pathology, University Hospital Zurich, Switzerland
Search for more papers by this authorE. Antonio Chiocca
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Neurosurgical Service, Massachusetts General Hospital, Boston, MA, USA
Search for more papers by this authorCorresponding Author
Xandra O. Breakefield
Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital, and Neurology Department, Harvard Medical School, Boston, MA, USA
Corresponding author: Dr. Xandra O. Breakefield, Massachusetts General Hospital East, Molecular Neurogenetics Unit, 13th St., Bldg. 149, Charlestown, MA 02129, USA Tel. +1 (617) 726–5728, Fax + 1 (617) 726–5736Search for more papers by this authorAbstract
Gene therapy has opened new doors for treatment of neoplastic diseases. This new approach seems very attractive, especially for glioblastomas, since treatment of these brain tumors has failed using conventional therapy regimens. Many different modes of gene therapy for brain tumors have been tested in culture and in vivo. Many of these approaches are based on previously established anti-neoplastic principles, like prodrug activating enzymes, inhibition of tumor neovascularization, and enhancement of the normally weak anti-tumor immune response. Delivery of genes to tumor cells has been mediated by a number of viral and synthetic vectors. The most widely used paradigm is based on the activation of ganciclovir to a cytotoxic compound by a viral enzyme, thymidine kinase, which is expressed by tumor cells, after the gene has been introduced by a retroviral vector. This paradigm has proven to be a potent therapy with minimal side effects in several rodent brain tumor models, and has proceeded to phase 1 clinical trials. In this review, current gene therapy strategies and vector systems for treatment of brain tumors will be described and discussed in light of further developments needed to make this new treatment modality clinically efficacious.
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