Chemical caspase inhibitors enhance cell culture viabilities and protein titer.
Mammalian cell cultures are integral to the production of therapeutic and diagnostic proteins. A common problem encountered in culturing these cell lines, however, is a loss in viability at later stages of the cell culture process. In this study the effects of three newly synthesized chemical caspase inhibitors were investigated for their capacity to inhibit cell death. Findings show that these protease inhibitors were successful in prolonging cellular viabilities among anchorage-dependent CHO-K1 and HEK-293 cells lines. Cells treated with one inhibitor, 7312, performed as well or better when compared with the commercially known caspase inhibitor, zVAD.fmk. Suspension CHO cells producing an IgG were used to investigate the capacity of 7312 to improve protein production. Treatment of cells with 7312 increased integrated cell densities by 33% with treated cells having a higher maximum cell density and higher viability. As a result, monoclonal antibody titers increased by 20% and higher in spinner flask experiments. Increasing productivity in mammalian cell cultures has key implications for the pharmaceutical and biotechnology sectors, which are presently focused on developing methods to enhance cell performance in bioreactor environments.
Arden
Nilou
N
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Ahn
Shin-Hyung
SH
Vaz
Wayne
W
Rhodes
Malcolm
M
Hancock
Christina
C
Abitorabi
M Abi
MA
Betenbaugh
Michael J
MJ
D000818:Animals; D016466:CHO Cells; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000378:metabolism*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins