Therapeutic and diagnostic methods relating to cancer stem cells
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.
1. A method for treating an individual having, cancer, comprising:
administering a therapeutically effective amount of a composition that targets a polypeptide encoded by a CSC-associated gene, wherein the composition is an isolated molecule that selectively binds to the polypeptide that is encoded by a CSC-associated gene and expressed on an ABCB5+ cancer stem cell of the individual, wherein the CSC-associated gene is Programmed Death-1 (PD-1), wherein the isolated molecule is conjugated to a therapeutic agent, and, wherein the isolated molecule is an antibody or antigen binding fragment, wherein the composition inhibits the activity of the ABCB5+ cancer stem cell, and wherein the cancer is a melanoma.
2. The method of claim 1 , wherein the therapeutic agent is selected from: a toxin and a chemotherapeutic agent.
3. The method of claim 2 , wherein the toxin is a radioisotope.
4. The method of claim 3 , wherein the radioisotope is selected from the group consisting of: 225Ac, 211At, 212Bi, 213Bi, 186Rh, 188Rh, 177Lu, 90Y, 131I, 67Cu, 125I, 123I, 77Br, 153Sm, 166Bo, 64Cu, 212Pb, 224Ra and 223Ra.
5. The method of claim 3 , wherein therapeutic agent is a chemotherapeutic agent.
6. The method of claim 1 , wherein the antibody or antigen-binding fragment is a monoclonal antibody, human antibody, chimeric antibody, humanized antibody, a single-chain antibody, F(ab′)2, Fab, Fd, Fv, or single-chain Fv fragment.
7. A method for treating an individual having, cancer, comprising:
administering a therapeutically effective amount of a composition that targets a polypeptide encoded by a CSC-associated gene, wherein the composition is an isolated molecule that selectively binds to the polypeptide encoded by a CSC-associated gene and expressed on an ABCB5+ cancer stem cell of the individual, wherein the CSC-associated gene is Programmed Death-1 (PD-1), wherein the isolated molecule is conjugated to a therapeutic agent, wherein the isolated molecule is an antibody or antigen binding fragment, wherein the composition inhibits the activity of the ABCB5+ cancer stem cell, and wherein the individual has been diagnosed with cancer by a method comprising the steps of:
(i) determining an expression level of a cancer stem cell (CSC)-associated gene on ABCB5+ cancer stem cell in a sample from an individual; wherein the CSC-associated gene is PD-1; and
(ii) comparing the expression level of the CSC-associated gene to a reference value from non-cancer samples,
wherein the higher expression of the CSC-associated gene on ABCB5+ cancer stem cell as compared to the reference value indicates a cancer.
8. A method for treating an individual having, cancer, comprising:
administering a therapeutically effective amount of a composition that targets a polypeptide encoded by a CSC-associated gene, wherein the composition is an isolated molecule that selectively binds to the polypeptide encoded by a CSC-associated gene and expressed on an ABCB5+ stem cell of the individual, wherein the CSC-associated gene is Programmed Death-1 (PD-1), wherein the isolated molecule is conjugated to a therapeutic agent, and, wherein the isolated molecule is an antibody or antigen binding fragment, wherein the composition inhibits the activity of the ABCB5+ cancer stem cell, and wherein the cancer is an ABCB5+ stem cell cancer.
9. The method of claim 7 , wherein the therapeutic agent is selected from: a toxin and a chemotherapeutic agent.
10. The method of claim 9 , wherein the toxin is a radioisotope.
11. The method of claim 10 , wherein the radioisotope is selected from the group consisting of: 225Ac, 211At, 212Bi, 213Bi, 186Rh, 188Rh, 177Lu, 90Y, 131I, 67Cu, 125I, 123I, 77Br, 153Sm, 166Bo, 64Cu, 212Pb, 224Ra and 223Ra.
12. The method of claim 9 , wherein therapeutic agent is a chemotherapeutic agent.
13. The method of claim 7 , wherein the antibody or antigen-binding fragment is a monoclonal antibody, human antibody, chimeric antibody, humanized antibody, a single-chain antibody, F(ab′)2, Fab, Fd, Fv, or single-chain Fv fragment.
14. The method of claim 8 , wherein the therapeutic agent is selected from: a toxin and a chemotherapeutic agent.
15. The method of claim 14 , wherein the toxin is a radioisotope.
16. The method of claim 15 , wherein the radioisotope is selected from the group consisting of: 225Ac, 211At, 212Bi, 213Bi, 186Rh, 188Rh, 177Lu, 90Y, 131I, 67Cu, 125I, 123I, 77Br, 153Sm, 166Bo, 64Cu, 212Pb, 224Ra and 223Ra.
17. The method of claim 14 , wherein therapeutic agent is a chemotherapeutic agent.
18. The method of claim 8 , wherein the antibody or antigen-binding fragment is a monoclonal antibody, human antibody, chimeric antibody, humanized antibody, a single-chain antibody, F(ab′)2, Fab, Fd, Fv, or single-chain Fv fragment.