Provided herein are methods for the production of antigen-specific effector T cells and NK cells from pluripotent stem cells which express a chimeric antigen receptor (CAR). Further provided herein are methods for the adoptive cell therapy by administering the effector T cells and/or NK cells provided herein.

Antigen-binding agents such as humanized antibodies or antigen-binding fragments thereof, that specifically bind to epidermal growth factor receptor variant III (EGFRvIII) are provided. The EGFRVIII-specific humanized antibodies or antigen-binding fragments thereof may be used for the treatment of cancer.

Provided are a fusion protein of an anti-TIGIT antibody and IL2 or a variant thereof, and an application thereof. Specifically, a fusion protein is provided, which comprises: (a) a first polypeptide comprising an anti-TIGIT antibody or an antigen-binding fragment thereof; and (b) a second polypeptide comprising interleukin-2 (IL-2) or a variant thereof having a lymphocyte growth promoting activity, the second polypeptide being fused to the first polypeptide. Also provided are an application of such a fusion protein in positively regulating immune cell activity and/or improving immune responses; and/or, an application thereof in the treatment of cancer, immunodeficiency or inflammatory diseases, or infectious diseases.

Disclosed herein are methods of eliciting an anti-cancer immune response by administering tumor-associated antigens, cells containing tumor-associated antigens, and/or nucleic acids encoding tumor-associated antigens. inducing immunogenic cell death in the cells expressing or containing the tumor-associated antigens. and optionally generating hyperactivated dendritic cells. Expression of tumor-associated antigens in a separate anatomical site generates a tumor avatar, which mimics the antigenic, but not immunosuppressive, environment of the tumor, with the generation of hyperactivated dendritic cells enhancing antigen presentation to elicit a robust anti-tumor T cell and antibody response. Also provided are compositions and kits containing nucleic acids and other components for use in the methods provided herein.

Fusion proteins comprising IL2 and IL2R (e.g., CIRB), IL2, IL2R and IL21R (e.g., CIRB21), and/or comprising IL2, IL2R, and CD28 (e.g., CIRB28); natural killer (NK) cells that express the fusion proteins and methods of use thereof, e.g., to treat subjects with cancer; and regulatory T cells (T-regs) that express a fusion protein comprising IL2, IL2R, and CD28 and methods of use thereof, e.g., to treat subjects with autoimmune disease or GVHD.

A method for culturing natural killer cells uses genetically modified T cells. The method for culturing natural killer cells, using genetically modified T cells enables the effective proliferation and production of natural killer cells from a smaller amount of source cells. In addition, the method enhances the cytolytic activity of natural killer cells. Therefore, the method for culturing natural killer cells, using genetically modified T cells may be suitable for various applications in commercializing cell therapy products. Further, the natural killer cells produced by the culturing method can be useful as a cell therapy product.

The presently disclosed subject matter provides methods and compositions for treating cancer (e.g., melanoma). It relates to chimeric antigen receptors (CARs) that specifically target MDA (e.g., Trp1), and immunoresponsive cells comprising such CARs. The presently disclosed MDA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a co-stimulatory signaling region having a mutated form of a cytoplasmic domain of DAP10 that enhances CAR-T cell function, e.g. by reducing CAR-T cell exhaustion. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The present disclosure provides, among other things, a cryopreservation medium comprising a cryoprotectant, an albumin, a disaccharide and a non-pyrogenic and isotonic crystalloid solution. The disclosure also provides, among other things, a cryopreservation medium for cryopreserving immune cells, the medium comprising: human serum albumin (HSA), sodium chloride, sodium gluconate, sodium acetate trihydrate, potassium chloride, magnesium chloride, dimethyl sulfoxide (DMSO), and a trehalose. The present disclosure also provides, a method of cryopreserving immune cells, transporting and subsequently administering such immune cells to a patient in need thereof.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. In various embodiments, the 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.