Use of a truncated CCN1 promoter for cancer diagnostics, therapeutics and theranostics

Patent metadata

Field	Value
Publication number	US-9750823-B2
Application number	US-201414895247-A
Country	US
Kind code	B2
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

Recombinant vectors in which expression of one or more elements (e.g. genes required for viral replication, detectable imaging agents, therapeutic agents, etc.) is driven by a truncated CCN 1 cancer selective promoter (tCCN1-Prom) are provided, as are cells and transgenic animals that contain such vectors. The vectors are used in cancer therapy and/or diagnostics, and the transgenic mice are used to monitor cancer progression, e.g. in screening assays.

First claim

We claim:

1. A recombinant vector comprising a truncated connective tissue growth factor/cysteine rich protein/nephroblastoma overexpressed gene-1 (CCN1) cancer selective promoter comprising the nucleotide sequence as set forth in SEQ ID NO: 1.

2. The recombinant vector of claim 1 , wherein said truncated CCN1 cancer selective promoter is operably linked to at least one gene of interest.

3. The recombinant vector of claim 1 , wherein said recombinant vector is a viral vector.

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

5. 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 a gene that is required for viral replication.

6. A mammalian cell comprising the recombinant vector according to claim 1 .

7. The cell of claim 6 , wherein said mammalian cell is a cancer cell.

8. A method of treating cancer in a patient in need thereof, comprising administering to said patient a composition comprising the recombinant vector of claim 5 , wherein said at least one gene of interest comprises a gene encoding an anticancer agent, wherein said anticancer agent is expressed in the subject at a level effective to exert an anticancer effect, and wherein said cancer is bladder cancer, brain cancer, breast carcinoma, cervical carcinoma, colorectal cancer, endometrial carcinoma, esophageal carcinoma, gastric cancer, gestational trophoblastic disease, hematopoietic cell cancer, hepatocarcinoma, lung cancer, melanoma, neuroblastoma, osteosarcoma, ovarian carcinoma, pancreatic cancer, prostate cancer, renal cancer, retinoblastoma, uterine sarcoma, vaginal carcinoma, or vulvar carcinoma.

9. The method of claim 8 , wherein the gene encoding the anticancer agent is a melanoma differentiation-associated 7/interleukin 24 (mda-7/IL-24) gene.

10. The method of claim 8 , wherein the vector is a viral vector and comprises a gene required for viral replication operably linked to a cancer-specific or cancer-selective promoter.

11. A method of imaging cancer in a patient in need thereof, comprising administering to said patient a composition comprising the recombinant vector of claim 5 , wherein said at least one gene of interest comprises a gene encoding an imaging agent, and detecting a signal from the imaging agent.

12. The method of claim 11 , wherein the vector is a non-viral vector.

13. The method of claim 11 , wherein the vector is a viral vector and further comprises a gene required for viral replication operably linked to a cancer-specific or cancer-selective promoter.

14. The recombinant vector of claim 5 , wherein the vector is a viral vector, and wherein the vector, in addition to the truncated CCN1 cancer selective promoter comprising SEQ ID NO: 1, further comprises one or more cancer-specific or cancer-selective promoters operably linked to a gene encoding one or more of an anticancer agent, an imaging agent, and a gene required for viral replication.

15. The vector of claim 14 , wherein the CCN1 cancer selective promoter is operably linked to gene encoding an anticancer agent.

16. The vector of claim 14 , wherein the CCN1 cancer selective promoter is operably linked to a gene encoding an imaging agent.

17. The vector of claim 14 , wherein the CCN1 cancer selective promoter is operably linked to a gene required for viral replication.

18. The vector of claim 14 , wherein at least one of the one or more cancer-specific or cancer-selective promoters is a progression elevated gene-1 promoter (PEG-Prom).

19. A nanoparticle comprising the vector of claim 5 .

Assignees

• Univ Virginia Commonwealth

Inventors

• Fisher Paul B
• Das Swadesh K
• Dash Rupesh
• Sarkar Devanand
• Sarkar Siddik
• Windle Jolene

Classifications

• A01K67/0275 Primary

  Genetically modified vertebrates, e.g. transgenic · CPC title

• C12N2830/008

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

• A61K49/005

  characterised by the carrier molecule carrying the fluorescent agent · CPC title

• C12N2830/34

  being a transcription initiation element · CPC title

• A01K2217/052

  inducing gain of function · CPC title