The current application fulfills a need for methods of making bi-specific CAR T-cells that have high efficacy. Aspects of the disclosure relate to a method for manufacturing a CD19/CD20 bi-specific chimeric antigen receptor (CAR) T cell comprising the ordered steps of: (a) providing a composition comprising a population of cells comprising T cells; (b) contacting the composition comprising the population of cells comprising T cells with one or more of a transactivating composition, IL-2, and/or IL-15; (c) transducing the cell composition from (b) with a CD19/CD20 bi-specific CAR nucleic acid; and (d) removing the transactivating composition from the cell composition of (c). Further aspects relate to a population of CD19/CD20 bi-specific CAR-T cells produced by the methods of the disclosure. Yet further aspects describe a method for treating a subject for B-cell lymphoma comprising administering cells of the disclosure.

Compositions and methods are provided for treating lymphoma in an individual by targeting engineered phagocytes to lymphoma cells. In particular, the phagocytes provided for administration to an individual, who has lymphoma, are engineered to express a chimeric antigen receptor (CAR) that specifically binds to an antigen present on lymphoma cells. The CAR localizes the engineered phagocytes to sites where lymphoma cells are present. In some embodiments, phagocytic activity of the phagocytes is enhanced by further engineering the phagocytes to express a hyperactive Rac GTPase.

Provided are chimeric antigen receptors having the hinge, transmembrane region, and/or intracellular domain of LILRB1, or functional fragments or variants thereof. Also provided herein are cells comprising the LILRB1 based receptors, and methods of making and using same.

The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

Methods and compositions for treating cancer, particularly improved CAR-T methods, are disclosed.

The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to a method for stimulating, priming and/or expanding in vivo T cells genetically modified to express a chimeric antigen receptor (CAR) targeted to an antigen, comprising contacting the T cells with the antigen or a variant thereof in vivo. In one embodiment, the antigen or variant thereof is provided by administering a nucleic acid encoding the antigen or variant thereof.

Down-regulating autoimmune regulator (AIRE) function in B cells to produce antibodies is described. The antibodies can be class-switched, high affinity, and neutralizing, and have a high degree of somatic hypermutations, even in the framework region, as compared to antibodies produced in the absence of AIRE downregulation.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

The invention provides improved compositions and methods for the treatment of solid cancers.