A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase

Cancer Gene Therapy
K CornettaD A Williams

Abstract

Administration of chemotherapy is often limited by myelosuppression. Expression of drug-resistance genes in hematopoietic cells has been proposed as a means to decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells were collected by apheresis and enriched for CD34+ expression. Nine subjects were infused with CD34+-enriched cells treated in a transduction procedure involving a 4-day exposure to cytokines with vector exposure on days 3 and 4. No major adverse event was related to the gene therapy procedure. Importantly, the engraftment kinetics of the treated product was similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo manipulation did not significantly reduce engrafting progenitor cell function. Gene-transduced cells were detected in all subjects. Although the level and duration was limited, patients receiving cells transduced using fibrone...Continue Reading

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Citations

Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Patrick F KellyDavid A Williams
May 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·J ShugaL G Griffith
Jan 29, 2014·Neuro-oncology·Johanna K Kaufmann, E Antonio Chiocca
Jun 26, 2007·The Journal of Pharmacology and Experimental Therapeutics·Jennifer L GoriR Scott McIvor
Mar 23, 2017·Hospital Pharmacy·Dominic A Solimando, J Aubrey Waddell
Feb 2, 2021·Neurosurgical Focus·Joshua L WangJ Bradley Elder

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