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High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system.

Authors :
Grein, Tanja A.
Loewe, Daniel
Dieken, Hauke
Salzig, Denise
Weidner, Tobias
Czermak, Peter
Source :
Biotechnology & Bioengineering; May2018, Vol. 115 Issue 5, p1186-1194, 9p
Publication Year :
2018

Abstract

Abstract: Oncolytic viruses offer new hope to millions of patients with incurable cancer. One promising class of oncolytic viruses is Measles virus, but its broad administration to cancer patients is currently hampered by the inability to produce the large amounts of virus needed for treatment (10<superscript>10</superscript>–10<superscript>12</superscript> virus particles per dose). Measles virus is unstable, leading to very low virus titers during production. The time of infection and time of harvest are therefore critical parameters in a Measles virus production process, and their optimization requires an accurate online monitoring system. We integrated a probe based on dielectric spectroscopy (DS) into a stirred tank reactor to characterize the Measles virus production process in adherent growing Vero cells. We found that DS could be used to monitor cell adhesion on the microcarrier and that the optimal virus harvest time correlated with the global maximum permittivity signal. In 16 independent bioreactor runs, the maximum Measles virus titer was achieved approximately 40 hr after the permittivity maximum. Compared to an uncontrolled Measles virus production process, the integration of DS increased the maximum virus concentration by more than three orders of magnitude. This was sufficient to achieve an active Measles virus concentration of > 10<superscript>10</superscript> TCID<subscript>50</subscript> ml<superscript>−1</superscript>. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00063592
Volume :
115
Issue :
5
Database :
Complementary Index
Journal :
Biotechnology & Bioengineering
Publication Type :
Academic Journal
Accession number :
128732163
Full Text :
https://doi.org/10.1002/bit.26538