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1. (WO2017189754) HSV--1 ONCOLYTIC VIRUS THERAPIES THAT SPECIFICALLYH KILL ALT DEPENDENT CANCERS

Pub. No.:    WO/2017/189754    International Application No.:    PCT/US2017/029683
Publication Date: Fri Nov 03 00:59:59 CET 2017 International Filing Date: Thu Apr 27 01:59:59 CEST 2017
IPC: A61K 35/763
C12N 7/00
A61P 35/00
Applicants: SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors: O'SHEA, Clodagh
DEHART, Jason
Title: HSV--1 ONCOLYTIC VIRUS THERAPIES THAT SPECIFICALLYH KILL ALT DEPENDENT CANCERS
Abstract:
Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICPO -deficient, such as by complete deletion of the ICPO gene, or mutation of the ICPO gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICPO. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.