Oncolytic tumor viruses and methods of use
AssigneeThe Salk Institute for Biological Studies
InventorsClodagh O'Shea, Shigeki Miyake-Stoner
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Abstract
Recombinant adenoviruses that selectively replicate in E2F deregulated tumor cells are described. The recombinant adenoviruses have a genome encoding a modified E1A protein, a modified or deleted E4orf1 protein, a modified or deleted E4orf6/7 protein, or any combination thereof, such that the recombinant adenoviruses exhibit replication defects in normal cells compared to tumor cells. In some instances, the recombinant adenovirus genomes encode additional modifications that target the recombinant adenoviruses to specific cell types, detarget the viruses from the liver, inhibit viral replication in the liver, and/or evade pre-existing neutralizing antibodies.
Claims26
A recombinant adenovirus, comprising:
- an adenovirus E1A promoter;
- an adenovirus E4 promoter;
- and
- a genome:
- encoding a modified E1A protein comprising a deletion of the LXCXE motif or a C124G substitution;
- and
- encoding a modified E4orf6/7 protein, wherein the function of the modified E4orf6/7 is impaired or abolished, or comprising a complete or partial deletion that results in the absence of E4orf6/7 protein expression;
- wherein the genome comprises a deletion of the entirety of each of the E3-RIDα/RIDβ and E3-14.7k coding sequences,
- wherein the recombinant adenovirus exhibits replication defects in normal cells compared to tumor cells and replicates to wild-type adenovirus levels in tumor cells.
Dependencies are inferred from the claim text.