Therapeutic and diagnostic methods relating to cancer stem cells

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.

1 - 75 . (canceled) 
     
     
         76 . An isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene set forth in Table 4, and that is conjugated to a therapeutic agent. 
     
     
         77 - 84 . (canceled) 
     
     
         85 . A composition comprising:
 an antibody or antigen binding fragment thereof that selectively binds to a polypeptide encoded by a CSC-associated gene expressed on an ABCB5+ cancer stem cell, wherein the CSC-associated gene is Programmed Death-1 (PD-1), wherein the antibody or antigen binding fragment is conjugated to a therapeutic agent selected from: a toxin and a chemotherapeutic agent, wherein the composition inhibits the activity of the ABCB5+ cancer stem cell.   
     
     
         86 . The composition of  claim 85 , wherein the toxin is a radioisotope. 
     
     
         87 . The composition of  claim 86 , 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. 
     
     
         88 . The composition of  claim 85 , wherein therapeutic agent is a chemotherapeutic agent. 
     
     
         89 . The composition of  claim 85 , 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.