Methods of cancer immunotherapy

Abstract

Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.

1 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of an isolated human pancreatic progenitor cell, wherein the isolated human pancreatic progenitor cell expresses insulin and betatrophin. 
     
     
         2 . The method of  claim 1 , wherein the isolated pancreatic progenitor cell further expresses C-peptide. 
     
     
         3 . The method of  claim 1 , wherein the isolated pancreatic progenitor cell further expresses Ngn3. 
     
     
         4 . The method of  claim 1 , wherein the isolated pancreatic progenitor cell further expresses C-peptide and Ngn3. 
     
     
         5 . The method of  claim 1 , wherein the differentiated cell is a progenitor cell. 
     
     
         6 . The method of  claim 5 , wherein the differentiated cell is a pancreatic progenitor cell. 
     
     
         7 . The method of  claim 1 , wherein the differentiated cell is a pluripotent stem cell. 
     
     
         8 . The method of  claim 1 , wherein the differentiated cell is an endodermal, mesodermal, or ectodermal progenitor cell. 
     
     
         9 . The method of  claim 1 , wherein the differentiated cell is a definitive endoderm progenitor cell. 
     
     
         10 . The method of  claim 1 , wherein the differentiated cell is a pancreatic endoderm progenitor cell. 
     
     
         11 . The method of  claim 1 , wherein the differentiated cell is a multipotent progenitor cell or an oligopotent progenitor cell. 
     
     
         12 . The method of  claim 1 , wherein the differentiated cell is a monopotent, bipotent, or tripotent progenitor cell. 
     
     
         13 . The method of  claim 1 , wherein the differentiated cell is an endocrine, exocrine, or duct progenitor cell. 
     
     
         14 . The method of  claim 1 , wherein the differentiated cell is a beta-cell. 
     
     
         15 . The method of  claim 1 , wherein the differentiated cell is an insulin-producing cell. 
     
     
         16 . The method of  claim 1 , wherein the administering comprises injecting the isolated pancreatic progenitor cell to the human in need thereof. 
     
     
         17 . The method of  claim 1 , wherein the administering comprises implanting the isolated pancreatic progenitor cell to the human in need thereof. 
     
     
         18 . The method of  claim 1 , wherein the cancer comprises a pancreatic cancer. 
     
     
         19 . The method of  claim 1 , wherein the cancer comprises a carcinoma. 
     
     
         20 . The method of  claim 1 , wherein the carcinoma comprises an adenocarcinoma or a choriocarcinoma. 
     
     
         21 . An isolated progenitor cell that expresses betatrophin, betatrophin mRNA, C-peptide, insulin, or any combination thereof, wherein the isolated progenitor cell is differentiated from a mammalian trophoblast stem cell. 
     
     
         22 . An isolated pancreatic progenitor cell, wherein the isolated pancreatic progenitor cell expresses one or more transcription factors selected from the group consisting of Foxa2, Pdx1, Ngn3, Ptf1a, and Nkx6.1. 
     
     
         23 . A method of treating a disease in a mammal in a subject in need thereof, the method comprising administering to the subject an isolated progenitor cell. 
     
     
         24 . A method of screening a substance for use in the treatment of a disease, the method comprising:
 a) contacting an isolated pancreatic progenitor cell with the substance; and   b) detecting a change in the level of at least one transcript or protein in the isolated pancreatic progenitor cell.   
     
     
         25 . A method of screening a substance for cellular modulation or cellular toxicity of a cell, the method comprising:
 a) contacting an isolated pancreatic progenitor cell with the substance;   b) determining a phenotypic or metabolic change in the isolated pancreatic progenitor cell that results from contact with the substance; and   c) correlating the change with cellular modulation.   
     
     
         26 . A method of producing insulin, betatrophin protein, or betatrophin mRNA, the method comprising contacting a mammalian trophoblast stem cell with one or more agents to activate miR-124, thereby producing a progenitor cell that secretes insulin in response to glucose stimulation or producing a progenitor cell that produces betatrophin protein or betatrophin mRNA.