The present disclosure provides methods and compositions related to Natural Killer T cells that are engineered to knock down the expression of one or more endogenous major histocompatibility complex (MHC) gene. The present disclosure also provides engineered CAR NKT cells that resist rejection by allogeneic immune cells both in vitro and in vivo.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Compositions and methods concern the sequence modification of an endogenous genomic DNA region. Certain aspects relate to a method for site-specific sequence modification of a target genomic DNA region in cells comprising: contacting the cells with an activating composition; transfecting the cells with a transfection composition comprising (a) donor DNA and (b) a DNA digesting agent; wherein the donor DNA comprises: (i) a homologous region comprising nucleic acid sequence homologous to the target genomic DNA region; and (ii) a sequence modification region; and wherein the genomic DNA sequence is modified specifically at the target genomic DNA region.

The present disclosure relates to combination therapies with Cbl-b inhibitor compounds, and compositions and kits comprising combinations with the Cbl-b compounds. Also provided are methods of using the combinations with Cbl-b compounds and compositions thereof, such as in therapeutic methods.

The present invention relates to the field of medicine, specifically the field of treatment of cancer. More specifically, the invention relates to a method for the ex vivo production of a population of highly functional NK cells from CD34-positive cells, to a population of highly functional NK cells obtained and to the use of such population of highly functional NK cells for adoptive cell therapy.

Embodiments of the disclosure encompass compositions comprising immune effector cells, such as natural killer (NK) cells, where the cells comprise one or more exogenously provided interleukins (IL), and wherein the cell optionally comprises one or more engineered receptors. In specific embodiments, the IL is not IL-15, and is IL-12, IL-21, or both. The NK cells may be utilized for treatment of cancer of any kind, including at least glioblastoma.

The present invention relates generally to immunotherapy. Disclosed herein are methods for obtaining cytolytic differentiated NKG2A.sup.−NKG2C.sup.+ cells with a given KIR specificity and also compositions comprising these cells as well as the use of these cells for therapy. The NK cell expansion methods provided herein also have non-therapeutic uses.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

The present invention relates to a method for inducing and proliferating target virus antigen-specific dual activated T cells, and can produce target virus antigen-specific dual activated T cells by treating monocytes, which are isolated from peripheral blood, with a cytokine and a virus antigen peptide mixture and culturing the same.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.