Modified parvovirus having enhanced anti-tumor efficacy

摘要

Described are parvovirus variants derived, e.g., from H-1PV, showing higher anti-tumor potential compared to the wild type parvovirus, wherein said variant is characterized by (a) an amino acid substitution, alteration or addition, preferably substitution at position Lys96 of NS-2 and/or position Leu103 of NS-2 (together with a amino acid substitution at position Tyr595 of NS-1 in the latter case), or (b) an in-frame deletion in the parvovirus genome, preferably a deletion resulting in a large amino acid deletion in both the central part (aa 96-133) of NS-2 and the C-terminal part (aa 587-624) of NS-1. The present invention also relates to the use of said parvovirus variants for cancer therapy.

主权项

1. A method for treating cancer, comprising the step of administering to a patient a parvovirus variant derived from parvovirus H-1 (H-1PV) or a related rodent parvovirus, wherein said variant (a) has an amino acid substitution at position Lys96 and/or position Leu103 of NS-2 in SEQ ID NO: 13, or (b) has an in-frame deletion consisting of from nucleotides 2022 to 2135 in SEQ ID NO: 11, resulting in the translation of an NS1 protein having a deletion of amino acids 587-624 in SEQ ID NO: 12 and an NS2 protein having a deletion of amino acids 96-133 in SEQ ID NO: 13.