Compositions and methods for treating or preventing t cell exhaustion
OwnerThomas H. Mann, Susan M. Kaechinventors
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Abstract
Provided herein are compositions and methods for treating or preventing T cell exhaustion in a subject. In particular, T cells expressing PKC theta K413R mutant or with disrupted CK1G2 activity are provided, which have improved T cell function and tumor control and which are resistant to T cell exhaustion.
Claims30
An isolated nucleic acid molecule comprising a nucleotide sequence encoding a mutant protein kinase C (PKC) theta protein, wherein the nucleotide sequence is operably linked to a heterologous nucleic acid.
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A method for treating or preventing T cell exhaustion in a subject in need thereof, comprising administering an effective amount of one or more modified immune cells to a subject, wherein the one or more modified immune cells comprises a nucleic acid molecule comprising the nucleotide sequence selected from the group consisting of:
- (a) a nucleotide sequence set forth in SEQ ID NO:
- 1;
- (b) a nucleotide sequence that encodes a polypeptide having the amino acid sequence set forth in SEQ ID NO:
- 2;
- and
- (c) a nucleotide sequence that is at least about 85% identical to the nucleotide sequences of (a) or (b), and which encodes a protein kinase C (PKC) theta protein comprising a K413R mutation.
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A modified immune cell comprising disrupted CK1G2 activity, wherein the modified immune cell has been contacted with an agent that disrupts CK1G2 activity selected from the group consisting of:
- an antisense oligonucleotide, a shRNA, a siRNA, a zinc finger nuclease, and CRISPR-Cas system.
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Dependencies are inferred from the claim text.