Natural killer cell products and methods
AssigneeBoard of Regents, The University of Texas System
InventorsJoseph Henri BAYLE, Xiaomei WANG, David Michael SPENCER, Wei-Chun CHANG
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Abstract
The technology relates generally to the field of immunology and relates in part to compositions and methods for growing and storing modified natural killer cells, including for example, conditional chemical regulation of natural killer cell function. The technology further relates to pharmaceutical compositions and treatment of subjects using modified natural killer cells.
Claims21
1-102. (canceled)
A nucleic acid, comprising a first polynucleotide and a second polynucleotide, wherein the first polynucleotide encodes a chimeric polypeptide comprising:
- (a) a ligand binding region;
- and
- (b) a signaling region, comprising:
- (i) a MyD88 polypeptide and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27, CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- or
- (ii) a truncated MyD88 polypeptide lacking the TIR domain and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27,
- CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- and wherein the second polynucleotide encodes an IL-15 polypeptide.
A modified natural killer (NK) cell comprising a nucleic acid comprising a first polynucleotide and a second polynucleotide, wherein the first polynucleotide encodes a chimeric polypeptide comprising:
- (a) a ligand binding region;
- and
- (b) a signaling region, comprising:
- (i) a MyD88 polypeptide and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27, CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- or
- (ii) a truncated MyD88 polypeptide lacking the TIR domain and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27, CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- and wherein the second polynucleotide encodes an IL-15 polypeptide.
A method of treating a subject diagnosed with cancer, the method comprising administering to the subject a modified natural killer (NK) cell comprising a nucleic acid comprising a first polynucleotide and a second polynucleotide, wherein the first polynucleotide encodes a chimeric polypeptide comprising:
- (a) a ligand binding region;
- and
- (b) a signaling region, comprising:
- (i) a MyD88 polypeptide and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27, CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- or
- (ii) a truncated MyD88 polypeptide lacking the TIR domain and a co-stimulatory polypeptide cytoplasmic signaling region selected from CD27, CD28, CD3, ICOS, 4-1 BB, CD40, RANK/TRANCE-R, and OX40;
- and
- wherein the second polynucleotide encodes an IL-15 polypeptide.
Dependencies are inferred from the claim text.