Abstract: The present invention provides a robust single clone Master Cell Bank (MCB) for an optimized production of H-1 parvovirus (H-1 PV) which is suitable to increase infectious parvovirus production compared to standard producer NB-324K mixed cells.

Abstract: The present invention provides a method for upstream optimization the large-scale parvovirus production, preferably the oncolytic protoparvovirus H-1 (H-1PV). It is based on microcarriers or macrocarriers and their respective use in suspension or fixed-bed, an optimized cell culture medium, and a medium exchange strategy. In summary, with the optimized cell culture medium and the new medium exchange strategy, the inventors established a reduction in seeded cell density and animal serum, leading to an animal serum-free harvest. The tested carriers are best suited for a high H-1PV yield, cell growth, and bead-to-bead transfer capability, wherein the inventors additionally scaled up the process from 24-well plates to Erlenmeyer, Spinner flask and iCellis nano. As a conclusion, the present invention provides a large-scale method for producing the oncolytic protoparvovirus H-1 with a high virus yield, while lowering production costs and avoiding undesired products of animal origin at the same time.

Abstract: The present invention relates to innovative protoparvoviruses (PV) expressing RNAi effectors, preferably shRNAs against the PD-L1 gene which display improved anticancer activity. These new viruses are based on the ?H-1PVsilencer platform that consists of a protoparvovirus H-1PV featuring an in-frame deletion within the NS region (?H-1PV) and harbouring a shRNA expression cassette in which the expression of the shRNA is controlled by the H1 Polymerase III promoter. In this invention the inventors aimed to use the ?H-1PVsilencer to silence the PD-L1 gene. PD1/PD-L1 negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to escape antigen-specific T cell immune responses. The present invention also provides cells or organisms comprising said parvovirus.

Abstract: The present invention concerns a pharmaceutical composition where a checkpoint inhibitor is combined with an oncolytic virus and the use of said combination for the treatment of cancer.

Abstract: Described is an optimized process for parvovirus production including an essentially serum-free medium which is suitable to increase parvovirus production compared to a standard medium, preferably for H-1PV production.

Abstract: The present invention provides a robust single clone Master Cell Bank (MCB) for an optimized production of H-1 parvovirus (H-1 PV) which is suitable to increase infectious parvovirus production compared to standard producer NB-324K mixed cells.

Abstract: Described is a parvovirus formulation which comprises (a) at least 1×109 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus such as LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) and (b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl2×2 H2O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium. A preferred use is the therapy of a brain tumour by intratumoral injection.

Abstract: The present invention provides a reproducible, effective and scalable process for the purification of (infectious) parvovirus H-1 particles. The purification process allows the separation of empty particles from particles containing a full genome and is compatible with large-scale H-1PV production for clinical applications.

Abstract: The present invention concerns a pharmaceutical composition where a checkpoint inhibitor is combined with an oncolytic virus and the use of said combination for the treatment of cancer.

Abstract: The present invention concerns a pharmaceutical composition where a checkpoint inhibitor is combined with an oncolytic virus and the use of said combination for the treatment of cancer.

Abstract: The present invention relates to innovative protoparvoviruses (PV) expressing RNAi effectors, preferably shRNAs, against the CDK9 gene which display improved anticancer activity. These new viruses are based on the ?H-1PVsilencer platform that consists of a protoparvovirus H-1PV featuring an in-frame deletion within the NS region (?H-IPV) and harbouring a shRNA expression cassette in which the expression of the shRNA is controlled by the HI Polymerase III promoter. In this invention the inventors aimed to use the ?H-1PVsilencer to silence the CDK9 gene whose activity is often dysregulated in cancer cells and known to contribute to tumorigenesis. The present invention also provides cells or organisms comprising said parvovirus.

Abstract: Described is a parvovirus formulation which comprises (a) at least 1×109 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus such as LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) and (b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl2×2 H2O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium. A preferred use is the therapy of a brain tumour by intratumoral injection.

Abstract: Described is a parvovirus formulation which comprises (a) at least 1×109 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus such as LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) and (b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl2×2 H2O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium. A preferred use is the therapy of a brain tumour by intratumoral injection.

Abstract: Described is the use of a parvovirus, preferably H-1PV, for the therapeutical elimination of cancer stem cells (CSCs), preferably neuroblastoma stem cells and glioblastoma stem cells.

Abstract: The present invention provides a reproducible, effective and scalable process for the purification of (infectious) parvovirus H-1 particles. The purification process allows the separation of empty particles from particles containing a full genome and is compatible with large-scale H-1PV production for clinical applications.

Abstract: Described is an optimized process for parvovirus production including an essentially serum-free medium which is suitable to increase parvovirus production compared to a standard medium, preferably for H-1PV production.

Abstract: The present invention concerns a pharmaceutical composition where a checkpoint inhibitor is combined with an oncolytic virus and the use of said combination for the treatment of cancer.

Abstract: Described is a reproducible, effective and scalable process for parvovirus production including characterization strategies, preferably production of H-1PV.

Abstract: Described are methods for efficiently down regulating the expression of a gene of interest in a cell by use of a modified rodent parvovirus that contains an expressible target specific nucleic acid, preferably an shRNA expression cassette. Also described are cells or organisms comprising said parvovirus.

Abstract: Described is a reproducible, effective and scalable process for parvovirus production including characterization strategies, preferably production of H-1PV.