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US 12,735,722 B2Granted
Oncolytic viruses encoding recombinant transforming growth factor (TGF)-beta monomers and uses thereof
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsGreg M. Delgoffe, Andrew P. Hinck, Kristin DePeaux
Life of this patent
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Abstract
Oncolytic viruses encoding a recombinant form of TGF-β engineered to prevent homodimerization and recruitment of TGF-β receptor I are described. The engineered TGF-β monomers function as dominant-negative TGF-β inhibitors. Oncolytic viruses encoding a TGF-β monomer can be used for cancer immunotherapy to inhibit the immunosuppressive tumor microenvironment.
Claims23
An oncolytic virus encoding a human recombinant transforming growth factor (TGF)-β monomer, wherein the human TGF-β monomer comprises:
- a leucine to arginine substitution at an amino acid residue corresponding to residue 51 of SEQ ID NO:
- 2;
- an alanine to lysine substitution at an amino acid residue corresponding to residue 74 of SEQ ID NO:
- 2;
- a cysteine to serine or a cysteine to arginine substitution at an amino acid residue corresponding to residue 77 of human TGF-β2 set forth as SEQ ID NO:
- 2;
- and
- a deletion of the α3 helix corresponding to amino acid residues 52-71 of human TGF-β2 set forth as SEQ ID NO:
- 2.
6 more elements
Dependencies are inferred from the claim text.