The present disclosure relates to a method for producing natural killer (NK) cells. More specifically, the present disclosure relates to a method for producing NK cells, characterized in that peripheral blood mononuclear cells from which CD3-positive cells are removed are proliferated together with feeder cells, and the peripheral blood mononuclear cells are re-stimulated with feeder cells at the time of reaching a specific accumulated population doubling level. The present disclosure also relates to a method for producing NK cells, characterized in that NK cells are cultured under appropriate culture conditions by using a bioreactor. The production method according to the present disclosure has an advantage that NK cells having a high cell-killing ability and cell survival rate can be produced with high purity and at high efficiency in a short period of time by a clinically friendly method as compared with existing methods, thereby increasing the productivity of an NK cell therapy agent.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

Provided are a composition for culturing NK cells, and a method of culturing NK cells using the same. According to an aspect, in culturing NK cells from peripheral blood mononuclear cells, when NK cells are cultured in a medium including the composition for culturing NK cells, the composition including IL-15, IL-18, and IL-27, the NK cells may proliferate in large quantities and activation of NK cells may be promoted. Therefore, when the NK cells are used, cancer cell apoptosis or cancer cell-killing ability may be promoted. Accordingly, the NK cells may be used as an effective adoptive immune cell therapy product in cancer prevention or treatment.

The present disclosure relates to methods that include the use of a first multi-chain chimeric polypeptide and a second multi-chain chimeric polypeptide for stimulating the NK cells, inducing or increasing proliferation of the NK cells, inducing differentiation of the NK cells, and treating a subject in need thereof using activated NK cells.

The present invention provides methods of expanding T cells from a non-haematopoietic tissue source. Further provided are compositions of expanded T cells and methods of using the expanded T cells (e.g., apart of an adoptive T cell therapy).

Methods and kits are provided for identifying subjects at increased risk for IgE mediated systemic inflammatory disorders, particularly asthma.

A method for producing natural killer cells is disclosed. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from a blood sample; isolating at least one of CD56+ cells and/or CD3/CD56+ cells from the PBMCs; and co-culturing the at least one of CD56+ cells and/or CD3/CD56+ cells with a combination of feeder cells in the presence of a cytokine. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

Cytokine induced memory like (CIML) NK cells with enhanced cytotoxicity are presented. Most typically, the CIML NK cells are derived from a mononuclear cell fraction of peripheral blood or cord blood. In further contemplated aspects, the CIML NK cells are expanded and induced in a contained and automated production environment that substantially reduces operational complexity and production cost.

Cytokine induced memory like (CIML) NK cells with enhanced cytotoxicity are presented. Most typically, the CIML NK cells are derived from a mononuclear cell fraction of peripheral blood or cord blood. In further contemplated aspects, the CIML NK cells are expanded and induced in a contained and automated production environment that substantially reduces operational complexity and production cost.

Provided herein are methods for pre-activating and expanding an isolated population of NK cells. Further provided herein are methods for the treatment of cancer by administering the pre-activated and expanded NK cells.