The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.

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. The method can further comprise freezing and thawing the CD56+ cells and/or CD3−/CD56+ cells. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

This invention relates to Natural Killer (NK) cell populations, to methods of producing the same and therapeutic applications thereof. More specifically, the invention relates to the expansion of NK cells by increasing the expression of specific transcription factors associated with NK cell production.

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Disclosed is a method of culturing natural killer cells (NK cells) applied to immunotherapy. More specifically, disclosed are a kit containing a medium for culturing NK cells (NKCM kit) that can efficiently amplify and activate NK cells effective for the treatment of malignant tumors by culturing lymphocytes derived from human peripheral blood, and a method of culturing natural killer cells using the kit. The method for amplifying NK cells of the present invention includes stimulating NK cells with lymphocytes separated from peripheral blood, culturing the NK cells in a medium containing IL-2, IL-12, IL-15, IL-17, IL-18, and IL-21, and isolating the NK cells. Provided is a pharmaceutical composition for cell therapy containing NK cells produced by the method of amplifying NK cells. The pharmaceutical composition for cell therapy is expected to be widely used to treat infections and/or cancer.

The present invention provides a chimeric antigen receptor and natural killer cells expressing the same, and particularly, a chimeric antigen receptor (CAR) which includes an intracellular signaling domain including the whole or a portion of an OX40 ligand (CD252), thereby having excellent effects of increasing anticancer activity of immune cells, and immune cells expressing the same.

The present invention relates to a method comprising the steps of provision of a sample derived from a blood sample of a subject that has received a checkpoint-inhibitor therapy and is suspected of developing or has developed symptoms of immune-related adverse events (irAE), adding a photosensitizing agent to the sample, and subjecting the sample to irradiation, which preferably generates immunoregulatory NK cells in said sample. In embodiments, the photosensitizing agent is 8-methoxypsoralen and/or the irradiation is UVA irradiation. In another aspect, the invention relates to immunoregulatory NK cells obtained from a method comprising the steps of provision of a sample derived from an isolated blood sample of a subject, adding a photosensitizing agent to the sample, and subjecting the sample to irradiation. Furthermore, the invention encompasses immunoregulatory NK cells for use in the treatment and/ or prevention of irAE in a subject that has received a checkpoint-inhibitor therapy.

Provided herein are methods of producing natural killer (NK) cells and/or ILC3 cells using a three-stage expansion and differentiation method with media comprising stem cell mobilizing factors. Also provided herein are methods of suppressing tumor cell proliferation using the NK cells and/or ILC3 cells and the NK cell and/or ILC3 cell populations produced by the three-stage methods described herein, as well as methods of treating individuals having cancer or a viral infection, comprising administering the NK cells and/or ILC3 cells and the NK cell and/or ILC3 cell populations produced by the three-stage methods described herein to an individual having the cancer or viral infection.

Natural killer cells are differentiated to an intraepithelial innate lymphoid cells (ielLC1)-like cell, with an increase in cytotoxic activity. Specifically, the disclosure provides a method for differentiating mammalian natural killer cells to adapt an ielLC1-like phenotype, the method comprising: differentiating peripheral natural killer (NK) cells in the presence of IL-15 and epithelial cells or plate coatings that mimic features of epithelial cells, to generate CD49a+ CD103+ cells having features and phenotype of ielLC1s, with enhanced cytotoxic activity and expression of Th1 type cytokines.

Strategies, systems, compositions, and methods for efficient production of knock-in cellular clones without reporter genes. An essential gene is targeted using a knock-in cassette that comprises an exogenous coding sequence for a gene product of interest (or “cargo sequence”) in frame with and downstream (3′) of an exogenous coding sequence or partial coding sequence of the essential gene. Undesired targeting events create a non-functional version of the essential gene, in essence a knock-out, which is “rescued” by correct integration of the knock-in cassette, which restores the essential gene coding region so that a functional gene product is produced and positions the cargo sequence in frame with and downstream of the essential gene coding sequence.