Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

This disclosure provides a method of identifying or separating activated regulatory T cells that have a demethylated Foxp3 TSDR region from a mixture of activated T cells. The mixture is depleted of cells bearing the CD154 molecule (CD40 ligand). The desired cells can be recovered using a Treg marker such as CD25, GITR, CTLA4, CD137, latent TGF-beta (LAP), GARP (LRRC32) or CD121a/b. The Treg cells having a demethylated Foxp3 TSDR region can be used, for example for preparation of pharmaceutical compositions for use in treatment.

Provided is an isolated nucleic acid molecule comprising a NKp30 transmembrane domain, and a chimeric antigen receptor comprising the same. The isolated nucleic acid molecule comprising a NKp30 transmembrane domain comprises nucleic acid sequences encoding (a) an extracellular antigen binding domain, comprising a heavy chain variable region; (b) a hinge domain; (c) a NKp30 transmembrane domain; and (d) a NKp30 cytoplasmic domain. By introducing nucleic acid sequences of the NKp30 transmembrane domain and the NKp30 cytoplasmic domain in combination with the extracellular antigen binding domain into a T cell, the resulting CAR-T cell is a multi-chain CAR-T cell with a NKp30 receptor complex. Consequently, the resulting CAR-T cell forms stable immune synapses with cancer cells and exhibits excellent cytotoxicity against cancer cells.

The present disclosure is directed to genome editing systems, reagents and methods for immunooncology.

The present disclosure relates in some aspects to methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and an immunomodulatory compound, such as a structural or functional analog or derivative of thalidomide and/or an inhibitor of E3-ubiquitin ligase. The provided methods, compositions and uses include those for combination therapies involving the administration or use of one or more immunomodulatory compounds in conjunction with a T cell therapy, such as a genetically engineered T cell therapy involving cells engineered with a recombinant receptor, such as chimeric antigen receptor (CAR)-expressing T cells. Also provided are compositions, methods of administration to subjects, articles of manufacture and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.

The present application relates to functionally improved third generation BCMA-CARs comprising modified intracellular co-stimulatory domains, which can be used in adoptive cell therapy, e.g., in treatment of diseases and disorders such as cancer.

Disclosed herein are genome-edited chimeric antigen receptor T cells (CAR-T), which can be derived from a cytotoxic T cells, a viral-specific cytotoxic T cell, memory T cells, or gamma delta () T cells, and comprise one or more chimeric antigen receptors (CARs) targeting one or more antigens, wherein the CAR-T cell is deficient in one or more antigens to which the one or more CARs specifically binds. In particular, the present disclosure relates to engineered mono, dual, and tandem chimeric antigen receptor (CAR)-bearing T cells (CAR-T) and methods of immunotherapy for the treatment of cancer.

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides novel bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma.