Modified immune cells having enhanced function and methods for screening for same
AssigneeThe Trustees of the University of Pennsylvania
InventorsYangbing Zhao, Jiangtao Ren
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Abstract
The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).
Claims6
A modified immune cell or precursor cell thereof, comprising:
- (A) an insertion and/or deletion in a gene locus encoding for a transcriptional modulator, wherein the insertion and/or deletion downregulates expression of the endogenous transcriptional modulator, wherein the transcriptional modulator is:
- (i) a transcription factor, SIX Homeobox 2 (SIX2) or Krüppel-like factor 4 (KLF4), wherein the insertion and/or deletion in the gene locus encoding for SIX2 or KLF4 downregulates gene expression of SIX2 or KLF4, and optionally downregulates gene expression of one or more downstream targets of SIX2 or KLF4 or
- (ii) an epigenetic regulator, histone-lysine-N-methyltransferase 2D (KMT2D) or PAXIP1 Associated Glutamate Rich Protein 1 (PAGR1);
- and
- (B) an exogenous T cell receptor (TCR) and/or chimeric antigen receptor (CAR) comprising affinity for an antigen on a target cell.
Dependencies are inferred from the claim text.