Recombinant vaccinia virus and methods of use thereof
The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus; and compositions comprising the replication-competent, recombinant oncolytic vaccinia virus. The present disclosure also provides use of the vaccinia virus or composition for inducing oncolysis in an individual having a tumor.
1. A replication-competent, recombinant oncolytic vaccinia virus comprising, in its genome, a nucleotide sequence encoding a variant interleukin 2 (IL-2v) polypeptide comprising the amino acid sequence of SEQ ID NO:9, wherein the nucleotide sequence encoding the variant IL-2v polypeptide comprises the nucleotide sequence of SEQ ID NO:10, SEQ ID NO:11, or SEQ ID NO:12.
2. The vaccinia virus of claim 1 , wherein the vaccinia virus comprises a modification to render the vaccinia thymidine kinase deficient.
3. The vaccinia virus of claim 2 , wherein the modification results in a lack of J2R expression and/or function.
4. The vaccinia virus of claim 1 , wherein the vaccinia virus is a Copenhagen strain vaccinia virus.
5. The vaccinia virus of claim 1 , wherein the vaccinia virus is a Western Reserve strain vaccinia virus.
6. The vaccinia virus of claim 1 , wherein the vaccinia virus comprises an A34R gene comprising a K151E substitution.
7. A composition comprising:
a) the vaccinia virus of claim 1 ; and
b) a pharmaceutically acceptable excipient.
8. The replication-competent, recombinant oncolytic vaccinia virus of claim 1 , wherein the nucleotide sequence encoding the variant interleukin 2 polypeptide comprises the nucleotide sequence of SEQ ID NO:10 or SEQ ID NO:12, and wherein the vaccinia virus is a Copenhagen strain vaccinia virus, is vaccinia thymidine kinase deficient, and comprises an A34R gene comprising a K151E substitution.
9. The replication-competent, recombinant oncolytic vaccinia virus of claim 8 , wherein the nucleotide sequence encoding the variant interleukin-2 polypeptide comprises the nucleotide sequence of SEQ ID NO:10.