Recombinant immune cells, methods of making, and methods of use

Abstract

A recombinant immune cell expresses a heterologous IgG Fc receptor. In some embodiments, the heterologous IgG Fc receptor can be a chimeric IgG Fc receptor. Generally, the chimeric IgG Fc receptor includes an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain generally includes a sufficient portion of CD64 to bind to an IgG Fc region. The intracellular domain of the chimeric IgG Fc receptor includes a sufficient portion of an Fc receptor allowing immunoreceptor tyrosine-based activation motif (ITAM) to initiate cell signaling when an IgG Fc region binds to the extracellular domain.

What is claimed is: 
     
         1 . A chimeric IgG Fc receptor comprising:
 an extracellular domain comprising a sufficient portion of CD64 to bind to an IgG Fc region;   a transmembrane domain; and   an intracellular domain comprising a sufficient portion of an Fc receptor immunoreceptor tyrosine-based activation motif (ITAM) to initiate cell signaling when an IgG Fc region binds to the extracellular domain.   
     
     
         2 . The chimeric IgG Fc receptor of  claim 1 , wherein the intracellular domain comprises at least a portion of the intracellular region of CD16A. 
     
     
         3 . The chimeric IgG Fc receptor of  claim 1 , wherein the intracellular domain comprises at least a portion of the intracellular region of CD27, CD28, CD134 (OX40), CD137 (4-1BB), FcεR1, NKG2D, CD244 (2B4), FcRγ, DAP10, DAP12, or CD3ζ. 
     
     
         4 . The chimeric IgG Fc receptor of any preceding claim, wherein the extracellular domain comprises the CD16A cleavage site. 
     
     
         5 . The chimeric IgG Fc receptor of any preceding claim, wherein the intracellular domain comprises a signaling domain. 
     
     
         6 . A polynucleotide encoding the chimeric receptor of any preceding claim. 
     
     
         7 . A recombinant cell comprising the polynucleotide of  claim 6 . 
     
     
         8 . A recombinant cell expressing the IgG Fc chimeric receptor of any one of  claims 1 - 5 . 
     
     
         9 . The recombinant cell of  claim 8 , wherein the recombinant cell is a natural killer (NK) cell. 
     
     
         10 . A recombinant natural killer (NK) cell comprising a polynucleotide that encodes CD64. 
     
     
         11 . A recombinant cell comprising a natural killer (NK) cell genetically modified to express CD64. 
     
     
         12 . A method of killing a tumor cell, the method comprising:
 contacting the tumor cell with an antibody that specifically binds to the tumor cell; and   contacting the tumor cell with the recombinant cell of any one of  claims 7 - 11  under conditions effective for the recombinant cell to kill the tumor cell.   
     
     
         13 . A method of treating a subject having a tumor, the method comprising:
 administering to the subject an antibody that specifically binds to cells of the tumor; and   administering to the subject a composition comprising the recombinant cell of any one of  claims 7 - 11  under conditions effective for the recombinant cell to kill cells of the tumor.   
     
     
         14 . A composition comprising:
 the recombinant cell of any one of  claims 7 - 11 ; and   an antibody bound to the chimeric receptor.   
     
     
         15 . A method of treating a subject having a tumor, the method comprising:
 administering to the subject the composition of  claim 14  wherein the antibody specifically binds to cells of the tumor.