Use of a truncated ccn1 promoter for cancer diagnostics, therapeutics and theranostics

Patent metadata

Field	Value
Publication number	US-2016101193-A1
Application number	US-201414895247-A
Country	US
Kind code	A1
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	Apr 14, 2016
Grant date	—

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 cancer cell comprising a recombinant truncated CCN1 cancer selective promoter having a nucleotide sequence as set forth in SEQ ID NO: 1.

2 . A recombinant vector comprising a truncated CCN1 cancer selective promoter having a nucleotide sequence as set forth in SEQ ID NO: 1.

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

4 . The recombinant vector of claim 2 or 3 , wherein said recombinant vector further comprises at least one promoter that is not truncated CCN1 and is operably linked to at least one additional gene of interest that is not said first gene of interest.

5 . The recombinant vector of any of claims 2 - 4 , wherein said recombinant vector is a viral vector.

6 . The recombinant vector of claim 5 , 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.

7 . The recombinant vector of any of claims 3 - 6 , wherein said at least one first gene of interest and said at least one additional 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.

8 . The recombinant vector of any of claims 2 - 7 , wherein said recombinant vector is present in a female transgenic mouse.

9 . A cell comprising a recombinant vector according to any of claims 2 - 7 .

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

11 . A female transgenic mouse, or offspring thereof, comprising a transgene under operational control of a cancer selective truncated CCN1 promoter.

12 . The female transgenic mouse of claim 11 , wherein said transgene encodes a detectable imaging agent.

13 . A female compound transgenic mouse, or offspring thereof, comprising
a transgene under operational control of a cancer selective truncated CCN1 promoter, wherein said transgene encodes a detectable imaging agent, and a transgene or genetic mutation that renders said female compound transgenic mouse, or offspring thereof, prone to develop cancer and/or metastatic cancer.

14 . A method of non-invasively imaging cancer cells and metastases in a female transgenic mouse that develops cancer, comprising
i) providing a transgenic mouse by genetically engineering a mouse to contain and express a detectable imaging agent under operational control of a cancer selective truncated CCN1 promoter; ii) providing at least one female compound transgenic mouse by breeding the transgenic mouse provided in step i) to a mouse that is genetically prone to develop cancer; and iii) non-invasively imaging cancer cells in said at least one female compound transgenic mouse by detecting expression of said detectable imaging agent in cancer cells of said at least one female compound transgenic mouse.

15 . The method of claim 14 further comprising the steps of
if cancer cells are detected in said detecting step, administering a candidate anti-cancer agent to said compound transgenic mouse; then
repeating said step of detecting cancer cells; and, if no or fewer cancer cells are detected in said repeating step than in said detecting step, then,
concluding that said candidate anti-cancer agent is an effective anti-cancer agent; and/or
if cancer cells are detected in said detecting step, administering a candidate anti-cancer agent to said compound transgenic mouse; then
repeating said step of detecting cancer cells; and, if the same or more cancer cells are detected in said repeating step than in said detecting step, then,
concluding that said candidate anti-cancer agent is not an effective anti-cancer agent.

16 . The method of claim 14 , further comprising the steps of
if cancer cells are not detected in said female transgenic mouse, administering a candidate anti-cancer cancer agent to said compound female transgenic mouse; repeating said step of detecting cancer cells after a time period during which said transgenic mouse would develop cancer; and, if no cancer cells are detected in said repeating step or if fewer cancer cells are detected in said repeating step than would be predicted in the absence of said candidate anti-cancer cancer agent, then, concluding that said candidate anti-cancer agent is an effective cancer prevention agent.

17 . A method of treating and/or preventing and/or imaging cancer in a patient in need thereof, comprising
administering to said patient a composition comprising a recombinant vector of any of claims 3 - 7 .

18 . The method of claim 17 , wherein said cancer is breast cancer, cervical cancer, endometrial cancer, gestational trophoblastic disease, ovarian cancer, uterine sarcoma, vaginal cancer and vulvar cancer.

Assignees

• Univ Virginia Commonwealth

Inventors

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

Classifications

• C12N2830/34

  being a transcription initiation element · CPC title

• C12N2015/8572

  Animal models for proliferative diseases, e.g. comprising an oncogene · CPC title

• C12N15/86

  Viral vectors · CPC title

• A61K49/0008

  Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure · CPC title

• A61K49/005

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