Clinical scale production of an improved retroviral vector expressing the human multidrug resistance 1 gene (MDR1)

Bone Marrow Transplant. 2000 May:25 Suppl 2:S114-7. doi: 10.1038/sj.bmt.1702368.

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 x 10(6) infectious particles/ml) for clinical scale transduction of CD34+ cells. Results from the production runs and the applied biosafety concept are described.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Biotechnology
  • Cell Line
  • Genes, MDR*
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms / drug therapy
  • Neoplasms / therapy
  • Retroviridae / genetics*
  • Safety
  • Transplantation, Autologous

Substances

  • Antineoplastic Agents