Methods of inhibiting tumor cell aggressiveness using the microenvironment of human embryonic stem cells

• US 8,106,004 B2
• Filed: 03/10/2008
• Issued: 01/31/2012
• Est. Priority Date: 07/28/2006
• Status: Active Grant

• Current Assignee: Children's Memorial Hospital
• Original Assignee: Children's Memorial Hospital
• Inventors: Hendrix, Mary Jessica, Postovit, Lynne-Marie, Seftor, Richard Edward Barnet, Seftor, Elisabeth Ann
• Primary Examiner(s): CHEN, SHIN LIN
• Application Number:
  US12/045,134
• Publication Number:
  US 20090186801A1
• Time in Patent Office: 1,422 Days
• Field of Search: 514/2, 530/350, 435/325
• US Class Current: 514/2
• 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 Nodal activity in tumor cell growth or aggressive tumors, or both, in a mammal in need thereof comprising intratumorally administering an effective amount of an inhibitor of Nodal activity to the mammal, having at least one tumor cell growth or aggressive tumor, or both, having Nodal activity wherein the inhibitor is Lefty protein and wherein the Nodal activity is inhibited, wherein the Lefty protein is isolated from a microenvironment of human embryonic stem cells (“

hESC”

).

2. The method of claim 1, wherein the Lefty protein is substantially pure.

3. The method of claim 1, wherein the tumor cell growth or aggressive tumor, or both, having Nodal activity is melanoma.

4. The method of claim 1, wherein the tumor cell growth or aggressive tumor, or both, having Nodal activity is breast cancer.

5. The method of claim 1, wherein the Lefty protein inhibits Nodal activity in the tumor cell growth or aggressive tumor, or both, wherein apoptosis is increased, cell proliferation is decreased, vasculogenic mimicry is reduced, or any combination thereof.