Universal retargeting of oncolytic hsv
OwnerDavid Baillat, Matthew Mulveyinventors
Life of this patent
Estimating the term…
Abstract
Provided herein are bispecific adaptor proteins and their use for retargeting oncolytic HSV to target cells, such as tumor cells.
Claims84
A method of retargeting a recombinant herpes simplex virus (HSV) to a tumor cell expressing a TAA, the method comprising administering to a subject having the tumor cell,
- (a) the recombinant HSV, wherein the recombinant HSV comprises a nucleotide sequence encoding a heterologous ligand peptide;
- and
- (b) an isolated bispecific adaptor protein, wherein the bispecific adaptor protein comprises a first binding domain with binding specificity to the heterologous ligand peptide expressed by the recombinant HSV and a second binding domain with binding specificity to the TAA expressed by the tumor cell,
- wherein, the first binding domain of the bispecific adaptor protein binds the heterologous ligand peptide expressed by the recombinant HSV and the second binding domain of the bispecific adaptor protein binds the TAA expressed by the tumor cell, thereby retargeting the recombinant HSV to the tumor cell.
A method of treating a cancer in a subject, wherein a TAA is expressed by the cancer cell, the method comprising administering to the subject,
- (a) a recombinant HSV, wherein the recombinant HSV comprises a nucleotide sequence encoding a heterologous ligand peptide;
- and
- (b) an isolated bispecific adaptor protein, wherein the bispecific adaptor protein comprises a first binding domain with binding specificity to the heterologous ligand peptide expressed by the recombinant HSV and a second binding domain with binding specificity to the TAA expressed by the cancer cell,
- wherein, the first binding domain of the bispecific adaptor protein binds the heterologous ligand peptide expressed by the recombinant HSV, the second binding domain of the specific adaptor protein binds the TAA expressed by the cancer cell, and thereby causing oncolysis of the cancer cell.
A bispecific adaptor protein for retargeting a recombinant HSV to a tumor cell, wherein the bispecific adaptor protein comprises a first binding domain with binding specificity to a heterologous ligand peptide expressed by the recombinant HSV and a second binding domain with binding specificity to a TAA expressed by the tumor cell.
A kit comprising a recombinant HSV as described in any one of claims 1-93, an isolated adaptor protein of any one of claims 43-72, and instructions for use.
A recombinant HSV comprising a nucleotide sequence encoding a heterologous ligand peptide, wherein the heterologous ligand peptide comprises La protein or a fragment thereof, and wherein the nucleotide sequence encoding the heterologous ligand peptide is inserted into the recombinant HSV by inserting into or replacing a portion of replacing the wild type gD.
A recombinant HSV comprising a nucleotide sequence encoding a heterologous ligand peptide, wherein the heterologous ligand peptide comprises a leucine-zipper moiety, and wherein the nucleotide sequence encoding the heterologous ligand peptide is inserted into the recombinant HSV by inserting into or replacing a portion the wild type gD.
Dependencies are inferred from the claim text.