mda-9/syntenin promoter to image and treat metastatic cancer cells

Patent metadata

Field	Value
Publication number	US-9701985-B2
Application number	US-201414895579-A
Country	US
Kind code	B2
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

Recombinant vectors in which expression of one or more elements (e.g. gene required for viral replication, detectable imaging agents, therapeutic agents, etc.) is driven by an mda-9/syntenin (mda-9) cancer selective promoter are provided, as are cells and transgenic animals that contain such vectors. The vectors are used in cancer therapy and/or diagnostics, especially to visualize (image) and treat metastasis (including in rapid in vitro assays), and the transgenic mice are used to monitor cancer progression and/or the efficacy of candidate therapeutic agents in screening assays.

First claim

We claim:

1. A recombinant vector comprising a mda-9 cancer selective promoter comprising the sequence set forth in SEQ ID NO: 2, wherein said recombinant vector is a viral vector.

2. The recombinant vector of claim 1 , wherein said mda-9 cancer selective promoter is operably linked to at least one gene of interest.

3. The recombinant vector of claim 1 , wherein said viral vector is selected from the group consisting of: an adenoviral vector, a lentiviral vector, a herpes simplex virus, a measles virus, and a vaccinia virus.

4. The recombinant vector of claim 1 , wherein said recombinant vector is present in a nanoparticle carrier.

5. The recombinant vector of claim 4 , wherein said nanoparticle carrier comprises polyethyleneimine (PEI).

6. The recombinant vector of claim 2 , wherein said at least one gene of interest encodes one or more of an anticancer agent, an imaging agent, and at least one gene that is required for viral replication.

7. The recombinant vector of claim 1 , wherein said mda-9 cancer selective promoter comprises the sequence set forth in SEQ ID NO: 1.

8. A mammalian cell comprising the recombinant vector of claim 1 .

9. The mammalian cell of claim 8 , wherein said cell is a cancer cell.

10. A method of treating cancer and/or metastatic cancer in a patient in need thereof, comprising administering to said patient a composition comprising the recombinant vector of claim 6 , wherein said at least one gene of interest encodes an anticancer agent.

11. The method of claim 10 , wherein said cancer is selected from the group consisting of melanoma, brain cancer, breast cancer, liver cancer, esophageal cancer, cervical cancer, lung cancer, colon cancer, bladder cancer, uterine cancer, endometrial cancer, gastric cancer, pancreatic cancer, prostate cancer, neuroblastoma, sarcoma, and thyroid cancer.

12. The method of claim 10 , wherein said cancer is metastatic cancer.

13. An in vitro method for detecting cancerous and pre-cancerous cells in a biological sample from a patient, comprising administering to cells in said biological sample the recombinant vector of claim 6 , wherein said at least one gene of interest encodes an imaging agent.

14. The in vitro method of claim 13 , wherein said biological sample is blood.

15. The in vitro method of claim 13 , wherein said recombinant vector is formulated for administration as a nanoparticle.

16. The in vitro method of claim 15 , wherein said nanoparticle comprises polyethyleneimine (PEI).

17. The recombinant vector of claim 6 , wherein the recombinant vector is a viral vector, and wherein the vector, in addition to the mda-9 cancer selective promoter, comprises a second promoter operably linked to a gene encoding one or more of an anticancer agent, an imaging agent, and a gene required for viral replication.

18. The recombinant vector of claim 17 , wherein the vector comprises a third promoter operably linked to a gene encoding one or more of an anticancer agent, an imaging agent, and a gene required for viral replication; wherein the recombinant vector comprises at least one each of the anticancer agent, the imaging agent, and the gene required for viral replication.

19. The recombinant vector of claim 18 , wherein the anticancer agent is operably linked to the mda-9 cancer selective promoter.

20. A recombinant vector comprising a mda-9 cancer selective promoter comprising the sequence set forth in SEQ ID NO: 2, wherein said recombinant vector is a plasmid vector, wherein said mda-9 cancer selective promoter is operably linked to at least one gene of interest, and wherein said at least one gene of interest encodes one or more of an anticancer agent, an imaging agent.

21. The recombinant vector of claim 20 , wherein said recombinant vector is present in a nanoparticle carrier.

22. The recombinant vector of claim 21 , wherein said nanoparticle carrier comprises polyethyleneimine (PEI).

23. The recombinant vector of claim 20 , wherein said mda-9 cancer selective promoter comprises the sequence set forth in SEQ ID NO: 1.

24. The recombinant vector of claim 20 , wherein the vector, in addition to the mda-9 cancer selective promoter, comprises a second promoter operably linked to a gene encoding one or more of an anticancer agent and an imaging agent.

25. The recombinant vector of claim 24 , wherein the vector comprises a third promoter operably linked to a gene encoding one or more of an anticancer agent and an imaging agent.

26. The recombinant vector of claim 25 , wherein the anticancer agent is operably linked to the mda-9 cancer selective promoter.

Assignees

• Univ Virginia Commonwealth

Inventors

• Fisher Paul B
• Das Swadesh K
• Menezes Mitchell E
• Sarkar Devanand

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5088

  of vertebrates · CPC title

• C12N15/8509

  for producing genetically modified animals, e.g. transgenic · CPC title

• C12N2830/85

  mammalian · CPC title

• C12N2830/008

  cell type or tissue specific enhancer/promoter combination · CPC title