Perfusion cultures of human tumor cells: a scalable production platform for oncolytic adenoviral vectors.
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 x 10(11) 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.
Yuk
Inn H Y
IH
Onyx Pharmaceuticals, Inc., Richmond, California, USA. inn@alum.mit.edu
Olsen
Matthew M
MM
Geyer
Scott
S
Forestell
Sean P
SP
D000256:Adenoviridae / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification*; D019149:Bioreactors / Q000382:microbiology*; D001709:Biotechnology; D002452:Cell Count; D002470:Cell Survival; D005240:Feasibility Studies; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D010477:Perfusion