Identification of mutations in herpes simplex virus envelope glycoproteins that enable or enhance vector retargeting to novel non-HSV receptors
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJoseph C. Glorioso, III, Hiroaki Uchida, Justus B. Cohen
Life of this patent
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Abstract
In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.
Claims15
A method of killing a cancerous cell in vivo comprising contacting the cell with a mutant HSV vector comprising a modified glycoprotein B (gB) wherein,
- when the parental HSV vector is HSV1 K26GFP, the modified gB comprises a substitution at amino acid residues gB:D285 and gB:A549 or
- when the parental HSV vector is a homologous HSV-1 or HSV-2 vector, the modified gB comprises a substitution at amino acid residues gB:D285 and gB:A549 of the homologous HSV vector, wherein the gB:D285 residue correlates to X in VYPYXEFVL (SEQ ID NO:1) of HSV1 K26GFP and the gB:A549 residue correlates to X in KLNPNXIAS (SEQ ID NO:2) of HSV1 K26GFP, wherein the mutant HSV vector is administered intratumorally, and wherein the mutant HSV vector further comprises a non-native ligand capable of specifically binding epidermal growth factor receptor (EGFR) or carcinoembryonic antigen (CEA) incorporated into the viral envelope of the mutant HSV vector.
A method of killing a cancerous cell comprising contacting the cell with a mutant HSV vector comprising a modified glycoprotein B (gB) wherein,
- when the parental HSV vector is HSV1 K26GEP, the modified gB comprises a substitution at amino acid residues gB:D285 and gB:A549 or
- when the parental HSV vector is a homologous HSV-1 or HSV-2 vector, the modified gB comprises a substitution at amino acid residues gB:D285 and gB:A549 of the homologous HSV vector, wherein the gB:D285 residue correlates to X in VYPYXEFVL (SEQ ID NO:1) of HSV1 K26GFP and the gB:A549 residue correlates to X in KLNPNXIAS (SEQ ID NO:2) of HSV1 K26GFP, wherein the cancerous cell is in vitro.
Dependencies are inferred from the claim text.