Methods of Inhibiting Tumor Cell Aggressiveness Using The Microenvironment of Human Embryonic Stem Cells

• US 20090186801A1
• Filed: 03/10/2008
• Published: 07/23/2009
• Est. Priority Date: 07/28/2006
• Status: Active Grant

• Current Assignee: Children's Memorial Hospital
• Original Assignee: Children's Memorial Hospital
• Inventors: Postovit, Lynne Marie, Seftor, Richard Edward Barnet, Hendrix, Mary Jessica, Seftor, Elisabeth Ann
• Granted Patent: US 8,106,004 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]

Abstract

The invention provides compositions comprising one or more isolated factors from a microenvironment of human embryonic stem cells (hESCs), including, but not limited to, Lefty and inhibitors of Nodal. The invention also provides methods of utilizing factors derived from human embryonic stem cells (hESC) and their microenvironment to treat and prevent tumor formation and progression and to inhibit tumor cell aggressiveness. The invention further provides methods of inhibiting tumor cell growth and/or treating aggressive tumors in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of an inhibitor of Nodal activity.

Claims

1. A method of inhibiting tumor cell growth and/or treating aggressive tumors in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of an inhibitor of Nodal activity.

2. The method of claim 1, wherein the inhibitor is derived from a microenvironment of human embryonic stem cells.

3. The method of claim 2, wherein the inhibitor is hESC-derived Lefty.

4. The method of claim 3, wherein the hESC-derived Lefty is substantially pure.

5. The method of claim 1 wherein the inhibitor comprises a synthetic Lefty that is identical to hESC-derived Lefty.

6. The method of claim 1, wherein the tumor is melanoma.

7. The method of claim 1, wherein the tumor is breast cancer.

8. The method of claim 3, wherein the Lefty is administered intraveneously, intratumorally, or orally.

9. The method of claim 5, wherein the Lefty is administered intraveneously, intratumorally, or orally.

10. The method of claim 1, wherein the inhibitor inhibits tumor cell growth by inducing apoptosis, reducing proliferation, reducing vasculogenic mimicry, or any combination thereof.