US 2026/0209705 A1 · ENGINEERED NATURAL KILLER CELLS AND RELATED METHODS

Abstract

Some embodiments relate to a population of engineered natural killer cells, wherein the NK cells express at least one polypeptide selected from the group consisting of human leukocyte antigen E, human leukocyte antigen F, and human leukocyte antigen G. The NK cells comprise a genetically engineered disruption of one or more copies of endogenous β-2 microglobulin and a genetically engineered disruption of one or more copies of a human leukocyte antigen class II-related gene selected from the group consisting of regulatory factor X associated ankyrin containing protein, regulatory factor 5, regulatory factor X associated protein, and class II transactivator. A method of producing human pluripotent stem cell-derived engineered natural killer cells under feeder free conditions also is provided, as is a method of treating a disease or disorder in a subject by administering the NK cells to the subject.

Claims55

Dependent claims

A population of engineered natural killer (NK) cells, wherein the NK cells express at least one polypeptide selected from the group consisting of human leukocyte antigen E (HLA-E), human leukocyte antigen F (HLA-F), and human leukocyte antigen G (HLA-G);

wherein the NK cells comprise a genetically engineered disruption of one or more copies of endogenous β-2 microglobulin (B2M);
and
wherein the NK cells comprise a genetically engineered disruption of one or more copies of a human leukocyte antigen (HLA) class II-related gene selected from the group consisting of regulatory factor X associated ankyrin containing protein (RFXANK), regulatory factor 5 (RFX5), regulatory factor X associated protein (RFXAP), and class II transactivator (CIITA).

A method of producing human pluripotent stem cell-derived engineered natural killer (NK) cells under feeder free conditions, the method comprising

(a) culturing human pluripotent stem cells genetically engineered to disrupt one or more copies of endogenous β-2 microglobulin (B2M) and one or more copies of a human leukocyte antigen (HLA) class II-related gene selected from the group consisting of regulatory factor X associated ankyrin containing protein (RFXANK), regulatory factor 5 (RFX5), regulatory factor X associated protein (RFXAP), and class II transactivator (CIITA);
(b) differentiating the human pluripotent stem cells to precursor cells capable of differentiating to hematopoietic cell types, endothelial cell types, and/or mesodermal derivatives;
(c) differentiating the precursor cells to NK cells under feeder free conditions in a culture media comprising SCF, IL-7, IL-15, and FIt3L;
and
(d) culturing the NK cells in a culture media comprising IL-15 and IL-18, and in the presence of an antibody or ligand that binds a receptor on NK cells to promote activation of the NK cells,
thereby generating human pluripotent stem cell-derived engineered NK cells.

3 more elements

Dependencies are inferred from the claim text.

Engineered natural killer cells and related methods

Life of this patent

Engineered natural killer cells and related methods

Life of this patent

Abstract

Claims55