Development of a Serum-free Suspension Process
for the Production of a Conditionally Replicating Adenovirus using A549 Cells |
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Authors: | Robert Longley Jr Laurie Radzniak Marc Santoro Yung-Shyeng Tsao Russell G G Condon Peggy Lio Marcio Voloch Zhong Liu |
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Institution: | (1) Biotechnology Development, Schering-Plough Research Institute, U2-1300, 1011 Morris Avenue, Union, NJ 07083, USA |
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Abstract: | Conditionally replicating adenoviruses (CRAVs) are a group of recombinant human adenoviruses genetically engineered to replicate
in selected tissues, such as tumors. These viruses could potentially offer significant medicinal benefits, since the restrictive
replication of these viral vectors leads to the lysis of target cells without harm to the surrounding tissues. The in vitro
propagation and amplification of the CRAV vectors often requires special host cells with deregulated growth control pathways.
In order to develop an efficient cell culture process for the scaleable production of a CRAV vector, A549 cells, a human lung
carcinoma cell line normally cultured in adherent culture, were adapted to suspension culture. CRAV production was demonstrated
with the suspension-adapted A549 cells and a baseline production process was developed in shake flasks. The ability to scale-up
virus production was confirmed in stirred tank bioreactors. Molecular characterization of the suspension-adapted A549 cells
indicates no significant changes in cellular mechanisms related to adenovirus infection. |
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Keywords: | Adenovirus Recombinant adenovirus Gene therapy A549 cells Serum-free Suspension Conditionally replicating adenoviruses (CRAVs) |
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