P140K-modified hematopoietic stem cells

P140K-modified hematopoietic stem cells are an autologous cell and gene therapy designed to protect the bone marrow from the dose-limiting toxicities of alkylating chemotherapy, specifically in the treatment of high-grade gliomas. The therapy involves harvesting a patient's CD34+ hematopoietic stem cells and transducing them ex vivo with a viral vector (typically retroviral or lentiviral) that expresses a mutant version of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. This mutant, containing a P140K substitution, is resistant to O6-benzylguanine (O6BG), a small molecule inhibitor used to sensitize tumor cells to alkylating agents like temozolomide. By re-infusing these modified cells, clinicians can administer higher, more effective doses of chemotherapy and O6BG, as the gene-modified hematopoietic cells are protected from myelosuppression and can be selectively expanded in vivo. This approach aims to improve therapeutic outcomes for patients with glioblastoma multiforme and other refractory brain tumors.

Other names

MGMT P140K-modified hematopoietic stem cellsMGMT P140K-transduced CD34+ cellsP140K-MGMT-modified HSCsP-140K-MGMT-modified HSCsP 140K-MGMT-modified HSCsO6-methylguanine-DNA-methyltransferase P140K-modified hematopoietic stem cellsO-6-methylguanine-DNA-methyltransferase P140K-modified hematopoietic stem cellsO 6-methylguanine-DNA-methyltransferase P140K-modified hematopoietic stem cells