Abstract: The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising a chimeric antigen receptor (CAR). In particular aspects, CAR-expressing T-cells are producing using electroporation in conjunction with a transposon-based integration system to produce a population of CAR-expressing cells that require minimal ex vivo expansion or that can be directly administered to patients for disease (e.g., cancer) treatment.

Abstract: Chimeric antigen receptors (CARs) and CAR-expressing T cells are provided that can specifically target cells that express an elevated level of a target antigen. Likewise, methods for specifically targeting cells that express elevated levels of antigen (e.g., cancer cells) with CAR T-cell therapies are provided.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.

Abstract: Antibodies and antigen binding fragments thereof are provided that bind to T-cell receptors (e.g., TCR?), essentially independent of T-cell epitope specificity. Methods for manipulation of T-cells and methods of treatment using such antibodies are likewise provided.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.

Abstract: Disclosed herein are methods and compositions for modulating the expression of a HLA locus, including Natural Killer (NK) cells that lack expression of one or more classic HLA genes and comprise one or more exogenous sequences that express one or more non-classic HLA gene.

Abstract: Chimeric antigen receptor (CAR) polypeptides (and immune effector cells expressing the CARs) are provided comprising modified hinge domain sequences. Also provided are engineered antigen presenting cells (APCs) that express transgenes encoding target antigen and human leukocyte antigen (HLA). In further aspect, immune effector cells are provided that have been selected for elevated mitochondrial spare respiratory capacity.

Abstract: Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

Abstract: Chimeric antigen receptor (CAR) polypeptides are provided comprising an antigen binding domain; a hinge domain; a transmembrane domain and an intracellular signaling domain, wherein the CAR polypeptide binds to a target antigen and wherein the antigen binding domain comprises HCDR sequences from a first antibody that binds to the target antigen and LCDR sequences from a second antibody that binds to the target antigen. In certain aspects, the target antigen is CD123.

Abstract: Provided herein is a method of expanding clinically-relevant quantities of polyclonal ?? T cells that have anti-tumor, anti-viral, and anti-bacterial reactivity. Polyclonal ?? T cells can target a variety of tumors, including solid tumors as well as other conditions, such as viral and bacterial infections.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.

Abstract: The present invention is directed to mammalian bi-specific T cells and methods for using these bi-specific T cells. More specifically, the invention relates to a method of controlling administration of cancer antigen to a subject by providing bi-specific T cells that express a viral antigen T cell receptor and a cancer antigen-specific chimeric receptors and triggering their activation by also administering antigen-presenting T-cells which express viral antigen. These bi-specific T cell clones are a source of effector cells that persist in vivo in response to stimulation with viral antigen, leading to long-term function after their transfer to patients with cancer and autoimmune diseases.

Abstract: In some aspects, isolated transgenic cells (e.g., transgenic T cells) are provided that comprise or express a transgene and DHFRFS and/or TYMSSS. Methods for selecting transgeneic cells are also provided.

Abstract: Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.

Abstract: Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

Abstract: In some aspects, isolated transgenic cells (e.g., transgenic T cells) are provided that comprise or express a transgene and DHFRFS and/or TYMSSS. Methods for selecting transgenic cells are also provided.

Abstract: Antibodies and antigen binding fragments thereof are provided that bind to T-cell receptors (e.g., TCR?), essentially independent of T-cell epitope specificity. Methods for manipulation of T-cells and methods of treatment using such antibodies are likewise provided.

Abstract: Chimeric antigen receptor (CAR) constructs are provided that are able to selectively bind to specific protein complexes, such as HER1/HER3 heterodimer receptors. CAR T-cells comprising these constructs can be used to safely and efficiently target cancer cells expressing specific protein complexes.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.