NR4A-deficient cells expressing c-Jun and uses thereof
AssigneeLyell Immunopharma, Inc.
InventorsViola Lam, Rachel Christina Lynn
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods of promoting a persistent effector function of immune cells, comprising modifying the cells to overexpress c-Jun and reduced levels of a NR4A gene and/or protein. Also provided are modified cells, e.g., immune cell, which have been modified to overexpress c-Jun and express reduced levels of NR4A gene and/or protein. Overexpressing c-Jun and simultaneously reducing expression levels of a NR4A gene and/or protein leads to exhaustion/dysfunction resistant cells, which are apoptosis resistant and also immune checkpoint resistant, and also to the maintenance of anti-tumor function in tumor microenvironments.
Claims20
A cell composition comprising a population of modified immune cells that have (i) a reduced expression level of a gene and/or protein of a member of a nuclear receptor subfamily 4 group A (NR4A) family and (ii) an increased expression level of a c-Jun protein, wherein the member of the NR4A family is selected from the group consisting of a NR4A member 1 (NR4A1), NR4A member 2 (NR4A2), and NR4A member 3 (NR4A3), wherein the modified immune cells are T cells.
A cell composition comprising a cell which (a) expresses a ligand binding protein, (b) has an increased expression level of a c-Jun protein, and (b) has a reduced expression level of a gene and/or protein of a member of a nuclear receptor subfamily 4 group A (NR4A) family, wherein the cell has been modified with a gRNA comprising, consisting of, or consisting essentially of the sequence set forth in any one of set forth in any one of SEQ ID NO:
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Dependencies are inferred from the claim text.