Granted Patent
B2
US 12,680,075 · App. 18/050,290 · Granted Jul 14, 2026
Immune cells derived from induced pluripotent stem cell
C12N5/0636A01K67/0271C12N5/0635C12N15/85C12N2501/065C12N2501/42C12N2501/60C12N2501/602C12N2501/603C12N2501/604C12N2501/606C12N2501/608C12N2501/65C12N2506/11C12N2506/45
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Abstract
Embodiments disclosed here are production methods and compositions of engineered immune cells, such as B or T lymphocytes, from limited lineage myeloid progenitor cells, or from pluripotent stem cells, or from multilineage hematopoietic progenitor cells comprising the addition of various cell differentiation transcription factors and inhibiting epigenetic histone methylations in said cells.
Claims (14)
1 . An immune cell produced by a method comprising:
a) in vitro transfecting myeloid progenitor cells that are CD34+CD45+ with an exogenous gene coding copy of each of the following transcription factors: ETS-related gene (ERG), homeobox A9 (HOXA9), and retinoic acid receptor (RAR)-related orphan receptor alpha (RORA), wherein the transcription factors are expressed in the transfected cells to produce a population of multilineage hematopoietic progenitor cells that have myeloid and erythroid potential and have no lymphoid potential or lymphoid potential that is less than 5%;
b) inhibiting Enhancer of Zeste Homolog 1 (EZH1) expression in the resultant population of multilineage hematopoietic progenitor cells to expand lymphoid potential; and
c) differentiating the resultant population of multilineage hematopoietic progenitor cells in the presence of a notch ligand or supportive stroma or both to promote differentiation into the lymphoid lineage and production of T lymphocytes or B lymphocytes;
wherein the immune cell comprises an exogenous copy of each of the transcription factors ETS-related gene (ERG), homeobox A9 (HOXA9), and retinoic acid receptor (RAR)-related orphan receptor alpha (RORA), and wherein the EZH1 in the immune cell is inhibited.
2 . The immune cell of claim 1 , wherein the T lymphocyte is CD4/CD8 double positive or CD8 single positive T cell.
3 . The immune cell of claim 1 , wherein the immune cell has characteristics of definitive lymphoid cells.
4 . The immune cell of claim 1 , wherein the immune cell further comprises an exogenous copy of each of the following reprogramming factors: SOX4 and MYB.
5 . The immune cell of claim 1 , wherein the immune cell further comprises an exogenous copy of each of the following reprogramming factors: NFIA and DACH1.
6 . The immune cell of claim 1 , wherein the immune cell further comprises an exogenous copy of each of the following reprogramming factors OCT4, SOX2, KLF4, and optionally C-MYC.
7 . The immune cell of claim 1 , wherein the immune cell is further genetically modified to remove the native T cell receptor (TCR) locus, to delete class I or class II major histocompatibility complexes or both, to express non-canonical human leukocyte antigen (HLA)-G or HLA-E or both, or to edit endogenous HLA therein.
8 . A composition comprising a population of the immune cells of claim 1 .
9 . A method of treating cancer, autoimmune disorders, or hematological diseases, the method comprising administering the immune cell of claim 1 to a subject in need thereof.
10 . An ex vivo or in vitro method of improving in vivo engraftment of hematopoietic cells in a host, the method comprising transplanting the immune cell of claim 1 into the host.
Assignments (5)
LICENSE
Recorded Dec 19, 2024
From: BOSTON CHILDREN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 069735/0887 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 17, 2022
From: HOWARD HUGHES MEDICAL INSTITUTE
To: THE CHILDREN'S MEDICAL CENTER CORPORATION
Reel/Frame 061805/0277 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 17, 2022
From: VO, LINDA THUY
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 061805/0395 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 17, 2022
From: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
To: THE CHILDREN'S MEDICAL CENTER CORPORATION
Reel/Frame 061805/0391 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 17, 2022
From: DALEY, GEORGE
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 061805/0213 →
Continuity (3)
Provisional Application
62383984
· Sep 6, 2016
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