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autologous MGMTP140K lentiviral vector-transduced HSCs

A preparation of autologous CD34+ hematopoietic stem cells (HSCs) transduced with a lentiviral-based proviral vector encoding for MGMTP140K, a mutant version of the human DNA repair protein O6-alkylguanine-DNA methyltransferase (MGMT), with potential protective activity against myelosuppression. MGMTP140K is resistant to the MGMT inhibitor O6-benzylguanine (O6BG; BG). Upon administration of the autologous MGMTP140K lentiviral vector-transduced HSCs back into the patient, the HSCs expressing the BG-resistant mutant MGMT protein could, when used in combination with BG, protect the hematopoietic system against the hematopoietic toxicity of BG by enabling normal methyltransferase activity. This protects hematopoiesis and allows for temozolomide (TMZ) and BG chemotherapy without myelosuppression. MGMT repairs TMZ-induced DNA methylation. The MGMT inhibitor BG depletes MGMT and thereby maximizes TMZ-mediated anti-tumor response. The depletion of MGMT in hematopoietic cells leads to unacceptable bone marrow toxicity.
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Synonym:autologous P140K MGMT-positive hematopoietic stem cells
autologous P140K MGMT-transduced CD34+ cells
autologous P140K MGMT+ hematopoietic progenitor cells
autologous P140K-MGMT transfected HPCs
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