Therapeutic and diagnostic methods relating to cancer stem cells

Patent metadata

Field	Value
Publication number	US-2016009804-A1
Application number	US-201514868126-A
Country	US
Kind code	A1
Filing date	Sep 28, 2015
Priority date	Nov 14, 2008
Publication date	Jan 14, 2016
Grant date	—

Abstract

The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.

First claim

1 . A method, comprising:
determining an expression level of a cancer stem cell (CSC)-associated gene in an ABCB5+ stem cell sample of an individual, wherein the CSC-associated gene is PD-1; comparing the expression level of the CSC-associated gene to a reference value; and administering to the individual a PD-1 antibody based on the PD-1 levels in the ABCB5+ stem cell.

2 - 3 . (canceled)

4 . The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a mRNA that is encoded by the CSC-associated gene.

5 . The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a polypeptide that is encoded by the CSC-associated gene.

6 - 12 . (canceled)

13 . The method of claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a non-cancer reference sample, and wherein the expression level of the CSC-associated gene in the ABCB5+ stem cell sample is greater than the expression level of the CSC-associated gene in the non-cancer reference sample.

14 . (canceled)

15 . The method of claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a cancer reference sample, and wherein, the expression level of the CSC-associated gene is about equal to the expression level of the CSC-associated gene in the cancer reference sample.

16 . (canceled)

17 . The method of claim 4 , wherein the expression level of the CSC-associated gene in the ABCB5+ stem cell is at least 10% higher than the expression level of the CSC-associated gene in the non-cancer reference sample.

18 - 42 . (canceled)

43 . A method for treating an individual having cancer, comprising:
administering a therapeutically effective amount to treat the cancer of an isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene on the surface of an ABCB5+ stem cell of the individual, wherein the CSC-associated gene is PD-1.

44 . The method of claim 43 , wherein the cancer is melanoma, breast cancer, prostate cancer, colon cancer or lung cancer.

45 - 52 . (canceled)

53 . The method of claim 43 , wherein the isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene is conjugated to a therapeutic agent.

54 . The method of claim 43 , wherein the isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene is an antibody or antigen binding fragment.

55 . The method of claim 54 , wherein the antibody or antigen-binding fragment is a monoclonal antibody, polyclonal antibody, human antibody, chimeric antibody, humanized antibody, a single-chain antibody, F(ab′) 2 , Fab, Fd, Fv, or single-chain Fv fragment.

56 - 65 . (canceled)

66 . A method of delivering a therapeutic agent to a ABCB5+ cancer stem cell, comprising:
contacting an ABCB5+ cancer stem cell with an isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene conjugated to a therapeutic agent in an effective amount to deliver the therapeutic agent to the ABCB5+ cancer stem cell, wherein the CSC-associated gene is ABCB5 and wherein the therapeutic agent is a small interfering nucleic acid that inhibits expression of PD-1.

67 - 69 . (canceled)

70 . The method of claim 66 , wherein the ABCB5+ cancer stem cell is in vitro.

71 . The method of claim 7 , wherein the ABCB5+ cancer stem cell is in an individual.

72 - 84 . (canceled)

85 . The method of claim 66 , wherein the small interfering nucleic acid that inhibits expression of PD-1 is an siRNA.

86 . The method of claim 66 , wherein the small interfering nucleic acid that inhibits expression of PD-1 is an shRNA.

87 . The method of claim 71 , wherein the individual has cancer.

88 . The method of claim 54 , wherein the antibody further binds to ABCB5.

89 . The method of claim 54 , wherein the isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene is linked to a second antibody that selectively binds to a polypeptide encoded by a second CSC-associated gene, wherein the second CSC-associated gene is ABCB5.

90 . The method of claim 53 , wherein the therapeutic agent is an anti-ABCB5 mAb.

Assignees

• Brigham & Womens Hospital

Inventors

• Frank Markus H
• Frank Natasha Y

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/57555

  of the prostate · CPC title

• G01N33/57535

  of the large intestine, e.g. colon, rectum or anus · CPC title

• G01N33/57515

  of the breast · CPC title

• G01N33/5752

  of the lungs · CPC title