Tumor associated vaccines and compositions for disrupting tumor-derived immunosuppression for use in combination cancer immunotherapy
AssigneeCity of Hope
InventorsDon J. Diamond, Edwin Manuel
Life of this patent
Estimating the term…
Abstract
In one embodiment, a single modality cancer immunotherapy regimen that includes a therapeutic composition is provided. Such a therapeutic composition may include a Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth. In some aspects, the Salmonella strain is an attenuated Salmonella typhimurium strain. In other aspects, the immunosuppressive target is STAT3, IDO1, IDO2, Arginase 1, iNOS, CTLA-4, TGF-β, IL-10, pGE2 or VEGF. In one embodiment, the immunosuppressive target is IDO1 or Arg1 and the shRNA molecule is any one of SEQ ID NO:5-14.
Claims19
A composition comprising:
- a Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth;
- wherein the shRNA molecule is STAT3, (ARG1), or iNOS;
- and wherein the Salmonella strain is selected from the group consisting of YS1646 (ATCC #202165), RE88, SL7207, x8429, x8431 and x8468 IDO1.
A composition comprising:
- a first Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth;
- wherein the shRNA molecule comprises an shSTAT3 molecule selected from SEQ ID NO:
- 1-4;
- an shIDO molecule selected from SEQ ID NO:5-9;
- an shARG1 molecule selected from SEQ ID NO:
- 10-14;
- or an shiNOS molecule selected from SEQ ID NO:
- 15-19, and
- wherein the first Salmonella strain is selected from the group consisting of YS1646 (ATCC #202165), RE88, SL7207, x8429, X8431 and x8468 IDO1.
A method of suppressing tumor growth comprising:
- administering a therapeutically effective amount of a first composition to a subject, the first composition comprising an anti-immunosuppressive vector that disrupts tumor-derived immune suppression and suppresses tumor growth,
- wherein the anti-immunosuppressive vector comprises a Salmonella typhimurium strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target which suppresses tumor growth;
- wherein the shRNA molecule is STAT3, ARG1 or iNOS;
- and wherein the Salmonella strain is selected from the group consisting of YS1646 (ATCC #202165), RE88, SL7207, x8429, x8431 and x8468 IDO1.
Dependencies are inferred from the claim text.