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MGMT P140K-modified autologous hematopoietic stem cells
- Development stage
- Phase 1
- Lead developer
- Cincinnati Children's Hospital Medical Center
- Modality
- Stem Cell Therapies → Cell Therapies, Gene Therapies
- Administration
- Intravenous
01
Overview
MGMT P140K-modified autologous hematopoietic stem cells is an experimental cell-based gene therapy developed by the Children's Hospital Medical Center, Cincinnati, for the treatment of high-grade gliomas, including glioblastoma multiforme and anaplastic astrocytoma. The therapy involves harvesting a patient's own peripheral blood stem cells (CD34+), transducing them with a retroviral vector carrying a mutant version of the *MGMT* gene (P140K), and re-infusing them into the patient. The P140K mutation renders the O6-methylguanine-DNA methyltransferase (MGMT) protein resistant to O6-benzylguanine (O6BG), a drug used to sensitize tumor cells to the alkylating chemotherapy agent temozolomide (TMZ). By protecting the hematopoietic system from the myelosuppressive effects of the TMZ/O6BG combination, this approach enables the administration of intensified chemotherapy regimens to more effectively target the brain tumor while reducing hematologic toxicity.
- Other names
- MGMT P140K-modified stem cellsMGMT P140K-transduced CD34+ cells
02
Targets
MGMT P140K (O6-methylguanine-DNA methyltransferase (MGMT))
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