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US 12,680,075 B2Granted
Immune cells derived from induced pluripotent stem cell
AssigneesChildren's Medical Center Corporation, President and Fellows of Harvard College
InventorsLinda Thuy Vo, George Q. Daley
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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.
Claims10
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.
3 more elements
Dependencies are inferred from the claim text.