Abstract
Retroviral vectors are currently the most important and best characterized tools for ex vivo genetic modification of hematopoietic progenitor/stem cells. As a prerequisite for clinical applications, large volumes of high-titer vector supernatants have to be generated in compliance with ‘GMP’ guidelines. This goal can be reached using a carefully selected producer cell clone and a conventional large-scale cell culture system. The retroviral vector SF1m provides efficient expression of the human multidrug resistance 1 (MDR1) gene in hematopoietic progenitor/stem cells in vitro and in NOD/SCID mouse repopulating human cells in vivo. Currently, a clinical phase I/II study is in preparation to test whether intensified consolidation chemotherapy is enabled by autologous transplantation of peripheral blood progenitor/stem cells that have been genetically modified with SF1m. Using multi-tray cell factories >19 l of serum-free vector containing supernatant were generated from cells of a previously established SF1m-producer clone, based on the PG13 packaging cell line. Testing of the final samples revealed sufficient quality (>1.5 × 106 infectious particles/ml) for clinical scale transduction of CD34+ cells. Results from the production runs and the applied biosafety concept are described. Bone Marrow Transplantation (2000) 25, Suppl. 2, S114–S117.
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Eckert, HG., Kühlcke, K., Schilz, A. et al. Clinical scale production of an improved retroviral vector expressing the human multidrug resistance 1 gene (MDR1). Bone Marrow Transplant 25 (Suppl 2), S114–S117 (2000). https://doi.org/10.1038/sj.bmt.1702368
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DOI: https://doi.org/10.1038/sj.bmt.1702368
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