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

• US 8,669,239 B2
• Filed: 08/10/2012
• Issued: 03/11/2014
• Est. Priority Date: 07/28/2006
• Status: Active Grant

• Current Assignee: Ann & Robert H. Lurie Children's Hospital of Chicago
• Original Assignee: Ann & Robert H. Lurie Children's Hospital of Chicago
• Inventors: Hendrix, Mary Jessica, Postovit, Lynne-Marie, Seftor, Richard Edward Barnet, Seftor, Elisabeth Ann
• Primary Examiner(s): Bowman, Amy
• Application Number:
  US13/572,273
• Publication Number:
  US 20120322857A1
• Time in Patent Office: 578 Days
• Field of Search: None
• US Class Current: 514/44
• CPC Class Codes: A61K 35/54 Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57415 of breast
• CPC Class Codes: G01N 33/5743 of skin, e.g. melanoma
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

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 or treating aggressive tumors that have Nodal activity 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, wherein said inhibitor is an antisense nucleic acid, wherein said antisense nucleic acid is delivered to said tumor cell, wherein the inhibitor inhibits tumor cell growth or treats aggressive tumors, and wherein said inhibitor is a Notch inhibitor.

2. The method of claim 1, wherein the inhibitor blocks expression of Nodal protein.

3. The method of claim 1, wherein the Notch inhibitor is a Notch siRNA.

4. The method of claim 1, wherein the inhibitor is a Notch4 inhibitor.

5. The method of claim 4, wherein the inhibitor is a Notch4 siRNA.

6. The method of claim 1, wherein said antisense nucleic acid specifically binds to a Nodal nucleic acid.