Flavivirus replicon constructs for tumour therapy

Details Flavivirus replicon constructs for tumour therapy Flavivirus replicon constructs for tumour therapy

C - Chemistry, Metallurgy

12

N

C12N 15/86 (2006.01) A61K 35/76 (2006.01) A61K 38/19 (2006.01) A61K 48/00 (2006.01) A61P 35/00 (2006.01) C12N 5/10 (2006.01) C12N 7/01 (2006.01) C12N 15/27 (2006.01) C12N 15/33 (2006.01) C12N 15/40 (2006.01) C12N 5/06 (2006.01) C12N 5/08 (2006.01)

Patent

CA 2597655

A flaviviral replicon-based construct is provided for delivery and expression of granulocyte-macrophage colony stimulating factor to facilitate tumour therapy. In particular, the replicon construct encodes a Kunjin virus replicon having one or more mutations in an NS2A non-structural protein that induce enhanced levels of cellular IFN that synergize with recombinant granulocyte- macrophage colony stimulating factor delivered according to the invention. The construct may be administered intra-tumourally or peri-tumourally to an animal as DNA, RNA or packaged into a VLP, for the therapeutic and/or prophylactic treatment of tumours and cancers such as melanoma, lung carcinoma, cervical carcinoma, lung epithelial carcinoma, prostate cancer, breast cancer, renal carcinoma, colon cancer, epithelial cancers and mesothelioma.

L'invention concerne une construction à base de réplicons du flavivirus, destinée à l'administration et à l'expression du facteur stimulant les colonies de granulocytes-macrophages afin de faciliter la thérapie antitumorale. Plus précisément, cette construction à base de réplicons code pour un réplicon du virus Kunjin comprenant une ou plusieurs mutations au niveau d'une protéine non structurale NS2A induisant des niveaux élevés d'IFN cellulaire coopérant avec le facteur stimulant les colonies de granulocytes-macrophages administré selon l'invention. Cette construction peut être administrée par voie intratumorale ou péritumorale à un animale, comme de l'ADN ou l'ARN, ou à l'intérieur d'une VLP, pour le traitement thérapeutique et/ou préventif de tumeurs et de cancers, tels que le mélanome, le carcinome pulmonaire, le carcinome du col de l'utérus, le carcinome épithélial pulmonaire, le cancer de la prostate, le cancer du sein, le carcinome rénal, le cancer du côlon, les cancers épithéliaux et le mésothéliome.

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