Deutsches Krebsforschungszentrum

Ruprecht-Karls-Universitat Heidelberg

Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts

Ruprecht-Karls-Universitaet Heidelberg

Barbara Leuchs

Jean Rommelaere

Michael Dahm

Antonio Marchini

Karsten Geletneky

Ottheinz Krebs

Marcus Müller

Wolfgang Wick

Christel Herold-Mende

Christiane Dinsart

Nazim El-Andaloussi

Joerg Schlehofer

Assia Angelova

Olaf Witt

Sonja Kern

Jeannine Lacroix

Dirk Jager

Elisabeth Hedwig Deubzer

Veronika Frehtman

Jorg Schlehofer

Kathrin Kuerschner

Sebastian Lutz

Dirk Jäger

Jörg Schlehofer

Hedwig Elisabeth Deubzer

Marcus Muller

Silvia Münstermann

Andrea Kuck

Kathrin Kürschner

Monika Frank-Stohr

Mandy Roscher

Xavier Allaume

Anna Illarionova

Markus Riese

Max Endele

Min Li-Weber

Zoltan Kis

Jeaninne Lacroix

Peter Krammer

Andrea Kern

Silvia Münsterman

Monika Frank-STÖHR

Zoltán Kis

Anna Khodosevich

Junwei Li

Silvia Muensterman

Marcus Mueller

Martin Vogel

Karen Nieto

Anna-Paula De-Oliveira

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.

Optimized parvovirus H-1 production

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.

Cancer therapy with an oncolytic virus combined with a checkpoint inhibitor

Described is a parvovirus formulation which comprises (a) at least 1&#xd7;10pfu/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 CaCl&#xd7;2 HO, 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.

Parvovirus formulation for treating tumors

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.

Scalable process for oncolytic rat parvovirus H-1 production and purification based on isoelectric point-based elimination of empty particles

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.

Use of parvovirus for eliminating cancer stem cells (CSCs)

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

Method for large scale production and purification of parvovirus

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.

Modified parvovirus useful for gene silencing

Described is an adenovirus derived helper virus which may comprise the adenoviral DNA sequences for E2a, S4 (orf6), the VA1 RNA gene, and the parvovirus VP capsid gene unit. Also described is a method of efficiently preparing a recombinant parvovirus (particle) which is based on the use of various adenoviral derived helper viruses/vectors.

Adenovirus derived helper virus for enhancing recombinant parvovirus production

The present invention relates to a parvovirus for the treatment of mesenchymal tumors, preferably malignant bone tumors such as localized and metastasized bone tumors, in particular osteosarcoma and Ewing's sarcoma. A preferred parvovirus includes a replication competent parvovirus H-1PV.

Oncolytic virotherapy for the therapy of ewing'S sarcoma

Described is a parvovirus, in particular a H-IPV, that can be genetically retargeted through modification of its capsid, which is useful in cancer therapy.

Retargeting of rat parvovirus H-1PV to cancer cells through genetic engineering of its capsid

Described is an antibody or an antigen binding fragment thereof specifically binding to a full or empty H-1 parvovirus capsid. Such an antibody is useful for various diagnostic and therapeutic methods, e.g., for the detection/therapy of an H-1 parvovirus infection during pregnancy since parvovirus affects about 1 in 400 pregnancies and may cause fetal loss or fetal hydrops.

Antibody that binds to H-1 parvovirus

Growing community of inventors

Heidelberg, Germany

Barbara Leuchs