	US 11,920,130 B2
	Modified immune cells having enhanced function and methods for screening for same
Yangbing Zhao, Lumberton, NJ (US); and Jiangtao Ren, Philadelphia, PA (US)
Assigned to The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed by THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, Philadelphia, PA (US)
Filed on May 12, 2022, as Appl. No. 17/743,183.
Application 17/743,183 is a division of application No. 16/365,326, filed on Mar. 26, 2019, granted, now 11,447,769.
Claims priority of provisional application 62/648,722, filed on Mar. 27, 2018.
Prior Publication US 2023/0032532 A1, Feb. 2, 2023
Int. Cl. C12N 15/11 (2006.01); C12N 5/0783 (2010.01); C12N 9/22 (2006.01); C12N 15/10 (2006.01)

CPC C12N 15/11 (2013.01) [C12N 5/0636 (2013.01); C12N 9/22 (2013.01); C12N 15/1082 (2013.01); C12N 2310/20 (2017.05); C12N 2800/80 (2013.01)]

19 Claims

1. A method for generating a modified immune cell or precursor cell thereof, comprising:

a) introducing into the immune cell a first nucleic acid comprising a nucleic acid sequence encoding an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) comprising affinity for an antigen on a target cell; and

b) introducing into the immune cell one or more polypeptides and/or nucleic acids that downregulate a gene expression of an endogenous transcriptional modulator;

wherein the endogenous transcriptional modulator is downregulated with a CRISPR system-mediated insertion and/or deletion in a gene locus encoding for the endogenous transcriptional modulator; and

wherein the endogenous transcriptional modulator is selected from the group consisting of AZI2, Clorf141, CCDC33, CCL7, CEACAM19, KLF4, MFSD5, PAGR1, SIX2, and USP27X.