Tangential Flow Filtration for the Concentration of Oncolytic Measles Virus: The Influence of Filter Properties and the Cell Culture Medium

Abstract

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.