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Oncolytic viruses and therapeutic molecules

A technology of oncolytic virus and virus, applied in the direction of virus, virus/bacteriophage, double-stranded DNA virus, etc., can solve the problem of tumor regression

Pending Publication Date: 2019-08-23
TRANSGENE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In vivo efficacy studies of a CDA enzyme inhibitor (ER-876437) and gemcitabine in an A2780 human ovarian cancer xenograft model showed that ER-876437 alone and gemcitabine alone had no effect on tumor growth when administered 30 minutes before gemcitabine ER-876437 caused complete and partial tumor regression in 10% and 30% of mice evaluated, respectively

Method used

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  • Oncolytic viruses and therapeutic molecules
  • Oncolytic viruses and therapeutic molecules
  • Oncolytic viruses and therapeutic molecules

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Experimental program
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Embodiment

[0181] Materials & Methods

[0182] virus and cell

[0183] All recombinant viruses used in this study were vaccinia viruses derived from the Copenhagen strain with a double deletion of thymidine kinase (J2R) and ribonucleotide reductase (I4L). VVTK-RR- / GFP is a double-deleted vaccinia virus expressing the gene marker GFP (green fluorescent protein). VVTK-RR- / CDD1 is a double-deleted vaccinia virus expressing the yeast cytidine deaminase CDD1 gene (Kurtz et al., 1999, Curr. Genet., 36(3):130-6). VVTK-RR- / hCD is a double-deleted vaccinia virus expressing the human cytidine deaminase CDA cDNA (Laliberté et Momparler, 1994, Cancer Res., 54(20):5401-7). VVTK-RR- / APOBEC2 is a double-deleted vaccinia virus expressing the human APOBEC2 gene. The GFP, CCD1, hCD and APOBEC2 genes were inserted into the thymidine kinase locus and placed under the control of the p11K.5 promoter. Virus structure was confirmed by multiplex PCR. The final recombinant vaccinia virus was amplified ...

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Abstract

The present invention relates to an oncolytic virus encoding a cytidine deaminase (CDAse) polypeptide, a composition comprising it, as well as their use for prophylactic or therapeutic purposes, and more particularly for the treatment of cancer. The present invention also provides a method for treating a disease or a pathologic condition comprising the administration of such an oncolytic virus orcomposition thereof and a process for preparing such an oncolytic virus.

Description

technical field [0001] The invention belongs to the field of oncolytic virus and therapeutic gene. The invention provides oncolytic viruses comprising one or more therapeutic genes. More specifically, the therapeutic genes of the invention are nucleoside pool modulators. More specifically, the nucleoside pool modulators of the invention are or have cytidine deaminase activity. The combination of an oncolytic virus with one or more therapeutic genes as defined herein confers enhanced anti-tumor efficacy on the oncolytic virus. The present invention finally provides oncolytic viruses for the prevention and / or treatment of proliferative diseases. Background technique [0002] Oncolytic viruses are a class of therapeutic agents with the unique property of tumor-dependent self-perpetuation (Hermiston et al., 2006, Curr. Opin. Mol. Ther., 8(4):322-30). The advantage of using these viruses is that as they replicate, they lyse host cells. Oncolytic viruses are capable of select...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/86A61K35/768A61P35/00C12N15/55
CPCC12Y305/04005C12N9/78C12N15/86C12N2710/24132C12N2710/24143C12N2710/24171A61K35/768A61P1/00A61P35/00A61P43/00A61P9/00Y02A50/30C12N7/00A61K9/0029A61K45/06C12N2710/24152
Inventor P·厄博斯J·弗洛派
Owner TRANSGENE SA
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