RECOMBINANT IMMUNE CELLS, METHODS OF MAKING, AND METHODS OF USE
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.
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.