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Production and purification of virus particles for the use in cancer therapy

: Grein, T.A.; Weidner, T.; Mühlebach, T.; Salzig, M.D.; Czermak, D.


New biotechnology 33 (2016), Supplement, pp.S33
ISSN: 1871-6784
European Congress on Biotechnology (ECB) <17, 2016, Krakow>
Fraunhofer IME ()

The knowledge about the oncolytic activity of viruses like measles opens up new possibilities in the effective treatment of incurable cancer. However, the successful therapy, requires high doses of oncolytic virus. In clinical trials the effective treatment dose was estimated with over 1011 TCID50 (50% tissue culture infectious dose) [Russel et al.]. Imagining the demand for cancer patients, currently used virus production systems like T-flasks or cell factories cannot provide for the required high virus doses.
However, besides the virus amount, also the stability has to be considered, as only active virus particles are suitable for cancer treatment. The measles virus is very sensitive towards temperature at cultivation conditions (half life approx. 1 h at 37 °C). Regarding the batch production process in cell factories, the virus particle can be harvest only once and, as the virus is released over a length of time, inactivation of virus particles will occur.
To ensure future therapy, this calls for an innovative bioprocess development that includes the integration of both efficient upstream and downstream processes with a suitable in-process control system.
Present study shows a new bioprocess concept for production and purification of oncolytic measles viruses for the use in cancer therapy. This approach not only increases virus yield by integration of a two-step virus purification system and online sensors, it also leads to decreased product contamination by e.g. host cell proteins and free DNA.