Vaccinia virus expression vector for selective replication in a tumor cell and introduction of exogenous nucleotide sequence into a tumor cell

• US 8,506,947 B2
• Filed: 02/16/2007
• Issued: 08/13/2013
• Est. Priority Date: 05/28/1999
• Status: Expired due to Term

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: United States Department Of Health And Human Services
• Inventors: McCart, J. Andrea, Bartlett, David L., Moss, Bernard
• Primary Examiner(s): Crouch, Deborah
• Application Number:
  US11/707,453
• Publication Number:
  US 20070154458A1
• Time in Patent Office: 2,370 Days
• Field of Search: None
• US Class Current: 424/93.1
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/24132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector

Abstract

A composition of matter comprising a vaccinia virus expression vector with a negative thymidine kinase phenotype and a negative vaccinia virus growth factor phenotype.

Claims

1. A method of introducing an exogenous nucleotide sequence into a mammalian tumor cell, comprising:

providing a composition comprising a vaccinia virus expression vector with a negative thymidine kinase phenotype and a negative vaccinia virus growth factor phenotype, wherein the vector selectively replicates in the tumor cells but is substantially incapable of replicating in non-dividing cells and wherein the vector has enhanced safety;

contacting said mammalian tumor cell with said composition; and

expressing said exogenous nucleotide sequence in the tumor cell, thereby producing an amount of an expression product.

2. The method of claim 1, wherein said exogenous nucleotide sequence encodes a polypeptide.

3. The method of claim 1, wherein the mammalian tumor cell is in a host, and wherein producing said amount of said expression product results in production of an antibody response by said host against said expression product.

4. The method of claim 1, wherein producing said amount of said expression product results in tumor cell death.

6. The method of claim 1, wherein the vaccinia virus expression vector is a VVDDEGFP expression vector.

7. The method of claim 1, wherein the mammalian tumor cell is a breast, colorectal, ovarian, pancreatic, melanoma, glioblastoma, hepatoma, small cell lung, non-small cell lung, muscle or prostate cell.

13. The method of claim 1, wherein said exogenous nucleotide sequence comprises a suicide gene.

14. The method of claim 13, wherein said suicide gene comprises cytosine deaminase.

15. The method of claim 13, wherein said suicide gene comprises carboxypeptidase G2.

16. The method of claim 1, wherein said exogenous nucleotide sequence comprises an imaging gene.

17. The method of claim 16, wherein said imaging gene comprises a somatostatin receptor.

18. The method of claim 16, wherein said imaging gene comprises a transferrin receptor.

19. The method of claim 1, wherein said exogenous nucleotide sequence comprises a tumor suppressor gene.

20. The method of claim 1, wherein said exogenous nucleotide sequence comprises a pathogenic antigen gene.

5. A method of inducing cell death of a dividing cancer cell, comprising contacting the dividing cancer cell with a composition comprising a vaccinia virus expression vector with a negative thymidine kinase phenotype and a negative vaccinia virus growth factor phenotype, thereby inducing cell death of the dividing cancer cell.

8. The method of claim 5, wherein the vaccinia virus expression vector is a VVDDEGFP expression vector.

9. The method of claim 5, wherein the dividing cancer cell is a mammalian tumor cell.

10. The method of claim 5, wherein the dividing cancer cell is a breast, colorectal, ovarian, pancreatic, melanoma, glioblastoma, hepatoma, small cell lung, non-small cell lung, muscle or prostate cell.

11. The method of claim 9, wherein contacting said dividing mammalian tumor cell with said composition is performed in vivo and said exogenous nucleotide sequence is expressed in vivo, thereby producing an amount of an expression product in vivo.

12. The method of claim 11, wherein the tumor cell comprises a dividing cancer cell, and wherein the method induces cell death of the dividing cancer cell in vivo.