NR4A super-repressors and methods of use thereof
AssigneeKSQ Therapeutics, Inc.
InventorsMichael Schlabach, Brian Alexander Sosa-Alvarado
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Abstract
The present disclosure provides super-repressors capable of inhibiting the transcription of NR4A1, NR4A2, and NR4A3 target genes. The super-repressors can be used to enhance the effector functions of immune cells, e.g., for adoptive cell therapy. Methods of treating disorders using the modified immune cells are also provided.
Claims19
A method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of cells comprising a polynucleotide comprising a nucleic acid encoding a polypeptide comprising a DNA-binding domain that specifically binds to both the NBRE element and the NurRE element, wherein
- (a) the polypeptide inhibits the activity of NR4A1, NR4A2, and NR4A3;
- or
- (b) the polypeptide is capable of inhibiting transcription of a gene operably associated with both the NBRE element and the NurRE element.
A method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of cells comprising a polynucleotide comprising a nucleic acid encoding a polypeptide comprising a DNA-binding domain that specifically binds to both the NBRE element and the NurRE element, wherein the polypeptide does not comprise a transcription activation domain.
Dependencies are inferred from the claim text.