Tangential Flow Filtration for the Concentration of Oncolytic Measles Virus: The Influence of Filter Properties and the Cell Culture Medium
by
Daniel Loewe 1,2
, Tanja A. Grein 1, Hauke Dieken 1, Tobias Weidner 1, Denise Salzig 1 and Peter Czermak 1,2,3,*
Daniel Loewe 1,2, Tanja A. Grein 1, Hauke Dieken 1, Tobias Weidner 1, Denise Salzig 1 and Peter Czermak 1,2,3,*
1
Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Wiesenstraße 14, 35390 Giessen, Germany
2
Faculty of Biology and Chemistry, University of Giessen, 35390 Giessen, Germany
3
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group Bioresources, Winchesterstr. 3, 35394 Giessen, Germany
*
Author to whom correspondence should be addressed.
Membranes 2019, 9(12), 160; https://doi.org/10.3390/membranes9120160
Received: 15 October 2019 / Revised: 21 November 2019 / Accepted: 26 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue EWM 2019: Membranes for a Sustainable Future)
The therapeutic use of oncolytic measles virus (MV) for cancer treatment requires >108 infectious MV particles per dose in a highly pure form. The concentration/purification of viruses is typically achieved by tangential flow filtration (TFF) but the efficiency of this process for the preparation of MV has not been tested in detail. We therefore investigated the influence of membrane material, feed composition, and pore size or molecular weight cut-off (MWCO) on the recovery of MV by TFF in concentration mode. We achieved the recovery of infectious MV particles using membranes with a MWCO ≤ 300 kDa regardless of the membrane material and whether or not serum was present in the feed. However, serum proteins in the medium affected membrane flux and promoted fouling. The severity of fouling was dependent on the membrane material, with the cellulose-based membrane showing the lowest susceptibility. We found that impurities such as proteins and host cell DNA were best depleted using membranes with a MWCO ≥ 300 kDa. We conclude that TFF in concentration mode is a robust unit operation to concentrate infectious MV particles while depleting impurities such as non-infectious MV particles, proteins, and host cell DNA.
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Keywords:
flat-sheet membrane; serum-containing medium; serum-free medium; membrane fouling; oncolytic virus; mathematical modeling; polyether sulfone; cross-linked regenerated cellulose
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MDPI and ACS Style
Loewe, D.; Grein, T.A.; Dieken, H.; Weidner, T.; Salzig, D.; Czermak, P. Tangential Flow Filtration for the Concentration of Oncolytic Measles Virus: The Influence of Filter Properties and the Cell Culture Medium. Membranes 2019, 9, 160.
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