A programmable receptor complex expressed by an immunocyte, wherein the programmable receptor complex includes a plurality of native or endogenously expressed receptor subunits, wherein the native or endogenously expressed receptor subunits have been engineered or modified to include FcRI receptor components, biotin-binding components, or both, and wherein the FcRI receptor components and biotin-binding components are operative to bind to target detector molecules that bind to or otherwise interact with predetermined targets.

A chimeric antigen receptor is provided, including an extracellular segment, including a single-chain antibody region binding to an antigen human CD19 and a hinge region, a trans-membrane segment, including a trans-membrane domain of human CD8 linked to the hinge region of the extracellular segment and embedded in cell membrane of T lymphocyte, and an intracellular segment, including an intracellular domain of human CD8, an intracellular domain of molecule 4-1BB and an intracellular domain of CD3 chain. The single-chain antibody region includes a heavy-chain variable region and a light-chain variable region of the single-chain antibody, the hinge region includes an extracellular domain of human CD8 alpha (CD8) of 55 amino acid residues and three alanine residues (AAA) located at the N-terminal of the extracellular domain of human CD8, and the intracellular domain of human CD8 includes seven amino acid residues and linked to the trans-membrane domain of human CD8.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Provided are methods, compositions and articles of manufacture for use in cell therapy involving the administration of one or more doses of a therapeutic T cell composition, and methods, compositions and articles of manufacture for use in the same. The cells of the T cell composition express recombinant receptors such as chimeric receptors, e.g. chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the embodiments of the present disclosure, including the dose of cells or units of cells administered and/or the phenotype of administered cells, provide various advantages, such as consistent dosing, lower risk of toxicity and/or increased response in subjects administered the T cell compositions.

Provided are polynucleotides encoding inactivated cell surface receptors. Also provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

Compositions comprising donor cells, acceptor cells, and methods involving the same are described herein. In some embodiments, the donor cell is deficient in at least one endogenous function, for instance cytotoxic activity. In some embodiments, the donor cell comprises a T cell receptor (TCR) and a cargo, and the acceptor cell comprises an MHC. In some embodiments, the TCR facilitates transfer of the cargo to the acceptor cell. In some embodiments, the donor cell comprises a chimeric antigen receptor (CAR) and a cargo, and the acceptor cell comprises an antigen bound by the CAR. In some embodiments, the CAR facilitates transfer of the cargo to the acceptor cell.

A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.