# US 2010/0169990 A1 · Compositions and methods for treating and diagnosing cancer

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- Number: US 2010/0169990 A1
- Document ID: US20100169990A1
- Status: Published application
- Kind: A1
- Application number: 12/650,873
- Filed: 2009-12-31
- Published: 2010-07-01
- Earliest claimed: 2005-10-31
- Assignees: The Regents of the University of Michigan
- Inventors: Michael F. Clarke; Tim Hoey; Xinhao Wang; Scott Dylla; Austin Gurney; Piero Dalerba; Grace Chen; Mark Prince
- Web page: https://patentgrep.com/patent/US20100169990A1

## CPC

- C12N 5/0695: {Stem cells; Progenitor cells; Precursor cells}
- C12N 5/0093: {Purging against cancer cells}
- Y10S 435/968: High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
- Y10S 435/971: Capture of complex after antigen-antibody reaction
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention relates to compositions and methods for characterizing, treating and diagnosing cancer. In particular, the present invention provides a cancer stem cell profile, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of cancer and in particular the targeting of solid tumor stem cells.

## Claims

### Claim 1

An isolated population of cancer stem cells obtained from a tumor of epithelial origin, wherein the population comprises at least 75% cancer stem cells and less than 25% non-tumorigenic tumor cells, wherein the cancer stem cells:
are tumorigenic; and,
express elevated levels of one or more of PTGFRN, CD166, CD164, CD82, TGFBR1, MET, EFNB2, ITGA6, TDGF1, HBEGF, ABCC4, ABCD3, TDE2, ITGB1, TNFRSF21, CD81, CD9, KIAA1324, CEACAM6, FZD6, FZD7, BMPR1A, JAG1, ITGAV, NOTCH2, SOX4, HES1, HES6, ATOH1, CDH1, EPHB2, MYB, MYC, SOX9, PCGF1, PCGF4, PCGF5, ALDH1A1, and STRAP, or reduced levels of one or both of TCF4 or VIM relative to the non-tumorigenic tumor cells.

### Claim 2 (depends on 1)

The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells are CD44+.

### Claim 3 (depends on 1)

The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells further express epithelial specific antigen (ESA).

### Claim 4 (depends on 1)

The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells are colon cancer stem cells.

### Claim 5 (depends on 1)

The isolated population of cancer stem cells of claim 1, wherein the cancer stem cells are head and neck cancer stem cells.

### Claim at position 6

6-10. (canceled)

### Claim 11

A method for obtaining from a tumor a cellular composition comprising cancer stem cells and non-tumorigenic tumor cells, wherein at least 75% are tumorigenic stem cells and 25% or less are non-tumorigenic tumor cells, said method comprising:
(a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;
(b) separating the mixture of tumor cells into a first fraction comprising at least 75% cancer stem cells and 25% or less non-tumorigenic tumor cells and a second fraction of tumor cells depleted of cancer stem cells wherein the separating is by contacting the mixture with reagents against CD44 and ESA; and
(c) demonstrating the first fraction to be tumorigenic by serial injection into a first host animal and the second fraction to be non-tumorigenic by serial injection into a second host animal.

### Claim 12 (depends on 11)

The method of claim 11 wherein the separating is performed by flow cytometry, fluorescence activated cell sorting (FACS), panning, affinity chromatography or magnetic selection.

### Claim 13 (depends on 11)

The method of claim 11 wherein the separating, is performed by fluorescence activated cell sorters (FACS) analysis.

### Claim 14 (depends on 11)

The method of claim 11 wherein the cancer stem cells are colon cancer stem cells.

### Claim 15 (depends on 11)

The method of claim 11 wherein the cancer stem cells are head and neck cancer stem cells.

### Claim 16

A method for enriching a population of cancer stem cells from a tumor of epithelial origin wherein the enriched population comprises 75% cancer stem cells and 25% or less non-tumorigenic tumor cells, said method comprising:
(a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;
(b) contacting the mixture of tumor cells with reagents against CD44 and ESA;
(c) selecting a first fraction of cancer stem cells by their binding to the reagents and a second fraction of colon tumor cells depleted of colon cancer stem cells; and
(d) demonstrating the first fraction to be tumorigenic by serial injection of the colon tumor stem cells into a host animal and the second fraction to be non-tumorigenic by serial injection into the host animal.

### Claim 17 (depends on 16)

The method of claim 16 wherein the selecting is performed by flow cytometry, fluorescence activated cell sorting (FACS), panning, affinity chromatography, or magnetic selection.

### Claim 18 (depends on 16)

The method of claim 16 wherein the selecting is performed by fluorescence activated cell sorters (FACS) analysis.

### Claim 19 (depends on 16)

The method of claim 16 wherein the cancer stem cells are colon cancer stem cells.

### Claim 20 (depends on 16)

The method of claim 16 wherein the cancer stem cells are head and neck cancer stem cells.

### Claim at position 17

-68. (canceled)