Methods to eliminate cancer stem cells by targeting cd47

Abstract

Described herein is the discovery that cancer stem cells (CSCs) can be induced to differentiate by altering CD47 signaling. Provided herein are methods and compositions for inducing differentiation of cancer stem cells, for instance irreversible differentiation, including methods of treating subjects with cancer such as breast cancer, colon cancer, lung cancer, ovarian cancer, or melanoma, and including metastatic as well as primary cancer. Also provided are methods for treating subjects with triple negative breast cancers involving forcing differentiation of bCSCs of the subjects through targeting of CD47.

1 - 16 . (canceled) 
     
     
         17 . A method for inducing differentiation of a cancer stem cell (CSC), comprising contacting the CSC with an antisense morpholino oligonucleotide complementary to CD47, thereby inducing differentiation of the CSC. 
     
     
         18 . The method of  claim 17 , wherein the differentiation of the CSC is SIRPα-independent. 
     
     
         19 . The method of  claim 17 , wherein the CSC expresses CD47. 
     
     
         20 . The method of  claim 17 , wherein the antisense morpholino oligonucleotide comprises the nucleic acid sequence of SEQ ID NO: 70. 
     
     
         21 . The method of  claim 20 , wherein the antisense morpholino oligonucleotide consists of the nucleic acid sequence of SEQ ID NO: 70. 
     
     
         22 . The method of  claim 17 , wherein the CSC comprises a breast cancer stem cell, a lung cancer stem cell, a prostate cancer stem cell, a colon carcinoma stem cell, or a melanoma stem cell. 
     
     
         23 . The method of  claim 17 , wherein the CSC is in a subject. 
     
     
         24 . The method of  claim 23 , wherein the contacting comprises administering the antisense morpholino oligonucleotide complementary to CD47 to a subject with cancer. 
     
     
         25 . The method of  claim 24 , wherein the subject has a primary tumor, has a tumor in regression, has or is suspected of having a metastatic tumor, or a combination thereof. 
     
     
         26 . The method of  claim 23 , further comprising administering a therapeutically effective amount of an anti-cancer treatment to the subject. 
     
     
         27 . The method of  claim 17 , wherein contacting the CSC is in vitro.