Modified stem cells keep glioblastoma at bay

Three patients with glioblastoma survived longer than predicted after they received transplants of their own blood stem cells that had been gene-modified to protect the bone marrow from the toxic effects of chemotherapy.

In the ongoing, small clinical trial described in Science Translational Medicine (2012;4[133]:133ra57), Hans-Peter Kiem, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and fellow researchers have been adding a modified version of the MGMT gene to the bone marrow stem cells of persons with glioblastoma, an invariably fatal brain cancer. MGMT can render tumor cells insensitive to chemotherapy and although the drug benzylguanine can block MGMT, the combination of chemotherapy and benzylguanine becomes too toxic for bone marrow cells, resulting in marrow suppression.

P140K is a modified version of MGMT that can repair the damage caused by chemotherapy and is unaffected by benzylguanine. Adding P140K to bone marrow stem cells in glioblastoma patients shields bone marrow cells while leaving tumor cells vulnerable.

Among glioblastoma patients with the MGMT gene who do not undergo such autologous transplants of gene-modified circulating blood stem cells, median survival is just over a year. The three patients in the Hutchinson study survived an average of 22 months posttransplant, with one patient still alive at 34 months. 

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