Immuno-oncolytic therapies
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorStephen Howard Thorne
Life of this patent
Estimating the term…
Abstract
The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and/or reduce host immunity and/or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and/or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.
Claims23
An oncolytic vaccinia virus comprising a nucleic acid encoding 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or a functional domain thereof, wherein the oncolytic virus is thymidine kinase negative.
A modified oncolytic vaccinia virus comprising an envelope with reduced sialylation relative to an otherwise identical unmodified virus, and a nucleic acid encoding for 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or a functional domain thereof, wherein the modified oncolytic vaccinia virus is thymidine kinase negative.
An oncolytic vaccinia virus comprising a nucleic acid encoding 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or a functional domain thereof and one or more of the following modifications:
- (i) a viral backbone mutation;
- (ii) a modification of viral glycosylation;
- (iii) a modification that promotes T cell response;
- (iv) a modification that inhibits immunosuppression;
- and
- (v) modification that enhances virus spread and activity,
- wherein the oncolytic vaccinia virus is thymidine kinase negative.
Dependencies are inferred from the claim text.