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Screening different host cell lines for the dynamic production of measles virus
Authors:Tanja A Grein  Felix Schwebel  Marco Kress  Daniel Loewe  Hauke Dieken  Denise Salzig  Tobias Weidner  Peter Czermak
Institution:1. Inst. of Bioprocess Engineering and Pharmaceutical Technology, Faculty of Live Science Engineering, University of Applied Sciences Mittelhessen, Giessen, Germany;2. Fraunhofer Inst. for Molecular Biology and Applied Ecology (IME), Project group Bioresources, Giessen, Germany;3. Dept. of Chemical Engineering, Kansas State University, Manhattan, KS
Abstract:Measles virus (MV) has a natural affinity for cancer cells and oncolytic MV preparations have therefore been investigated in several clinical trials as a potential treatment for cancer. The main bottleneck in the administration of oncolytic MV to cancer patients is the production process, because very large doses of virus particles are required for each treatment. Here, we investigated the productivity of different host cells and found that a high infection efficiency did not necessarily result in high virus yields because virus release is also dependent on the host cell. As well as producing large numbers of active MV particles, host cells must perform well in dynamic cultivation systems. In screening experiments, the highest productivity was achieved by Vero and BJAB cells, but only the Vero cells maintained their high virus productivity when transferred to a stirred tank reactor. We used dielectric spectroscopy as an online monitoring system to control the infection and harvest times, which are known to be critical process parameters. The precise control of these parameters allowed us to achieve higher virus titers with Vero cells in a stirred tank reactor than in a static cultivation system based on T‐flasks, with maximum titers of up to 1011 TCID50 ml?1. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:989–997, 2017
Keywords:oncolytic virus  measles virus  production process  online monitoring  dielectric spectroscopy
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