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Keywords:

  • oncolytic adenoviral vectors;
  • human tumor cells;
  • perfusion bioreactors;
  • high-density cell culture;
  • adenovirus production

Abstract

This study demonstrates the novel use of the HeLaS3 human tumor cell line for propagating ONYX-411, a recombinant oncolytic adenoviral vector. HeLaS3 cells enabled high levels of vector production without the risk of generating vector recombinants, which is possible with HEK293 cells. The development of a high-cell-density perfusion process using ATF technology yielded production levels as high as 6 × 1011 vp/mL, which was approximately sevenfold greater than the titers achieved in fed-batch bioreactors. Several experiments were performed at the bench (15 L) and pilot (70 L) scales to demonstrate the robust and scalable nature of this industrially relevant technology. © 2004 Wiley Periodicals, Inc.