Oncolytic measles viruses are identified as a promising and potent candidate for cancer treatments. However, for a successful treatment of patients suffering e.g. on multiple myeloma, more than 10<sup>11</sup> of infective virus particles are required. 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 to further fulfill GMP-standards.<br/>Since the measles virus shows a half-life time of just 1 h at 37°C, the virus production is hampered by the poor virus stability. As consequence, maximal yields of the instable product can only be achieved, if the optimal time of harvest (TOH) can be determined precisely. We integrated impedance spectroscopy in the production process for the determination of the optimal TOH. In 16 independent bioreactor runs, the maximum Measles virus titer was achieved approximately 40 h after the permittivity maximum.<br/>Standardization of the USP leads to a reduction of batch-to-batch variations which simplifies the optimization of the production to gain a maximum of infectious MV particles, followed by a highly efficient downstream processing. Purification steps have to lead in a minimum in product loss and a maximum in impurity removal, due to authority regulations. Therefore, the first clarification, based on depth filtration, and the finally chromatographic virus purification were investigated.

Production and purification of oncolytic measles viruses

255th National Meeting (2018)

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