There is provided herein a method for expanding human CD4?CD8? regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), prefer-ably the DN Tregs are ??-TCR?CD56? or alternatively ??-TCR+.

Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human T cell receptor alpha constant region gene. The present disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells.

Provided are methods and compositions for use in cancer immunotherapies. Exemplary compositions include functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. In some embodiments, derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

Disclosed herein are fusion proteins having a ?2M polypeptide and a presenting peptide, and nucleic acids that encode such fusion proteins. Provided herein are also genetically engineered cells expressing such fusion protein, methods of their production, and their uses in allogeneic transplant. CAR-T cells expressing fusion protein disclosed herein and their uses in cancer treatment are also disclosed.

Disclosed is a method for obtaining a population of human Treg cells including the steps of: (a) culturing a population of human monocytes with a medium including an amount of an interleukin-34 (IL-34) polypeptide in order to obtain a population of immunosuppressive macrophages; (b) co-culturing a population of human peripheral blood mononuclear cells (PBMCs) and the population of immunosuppressive macrophages obtained at step (a).

The present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).

A T cell product for administration to a subject and a use thereof are provided. The product includes at least one allogeneic T cell, which expresses at least one MHC molecule identified as an exogenous source by at least one T cell of the subject. The T cell product can widen the range of a donor and activate an immune response of the subject. The T cell product is used in the preparation of a drug for treating tumors.

Embodiments of the disclosure encompass methods for generating or expanding a population of immune cells specific for a virus, comprising stimulating immune cells specific for a virus by culturing peripheral blood mononuclear cells (PBMCs) in cell culture medium comprising human platelet lysate in the presence of: (i) one or more peptides corresponding to all or part of one or more antigens of the virus; or (ii) antigen presenting cells (APCs) presenting one or more peptides corresponding to all or part of one or more antigens of the virus. In particular embodiments, the cell culture medium comprises a particular percentage of human platelet lysate and/or the PBMCs are depleted of CD45RA-positive cells, for example.

The present application relates to a modified immune effector cell, wherein the functions of a T cell antigen receptor (TCR) and major histocompatibility complexes (MHCI, MHCII) in the modified immune effector cell are inhibited in a T cell, and the modified immune effector cell comprises a chimeric antigen receptor (CAR) targeting IL13R2. The modified immune effector cell of the present application knocks out TCR and HLA-A genes expressed by the cell while recognizing surface antigens of tumor cells, so that multiple effects of improving the anti-tumor effect of CAR-T cells, prolonging the survival time of the cells, and reducing the immune rejection response caused by allogeneic cell therapy are achieved.

Provided herein, among other things, are anti-CD 19 chimeric antigen receptor (CAR)s and natural killer cells expressing the same.