The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

The present invention provides therapeutics for the treatment of Multiple myeloma. In particular, the present invention provides chimeric antigen receptor (CAR) T-cells that can target the B cell maturation antigen.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

Provided herein are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain plasma cell malignancy. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for treating subjects with multiple myeloma (MM). Also provided are genetically engineered cells containing such BCMA-binding receptors for uses in adoptive cell therapy.

Aspects of the invention include compositions and methods for treatment of hematological tumors with engineered or non-engineered γδ-T cells. In some embodiments, the γδ-T cells comprise a chimeric antigen receptor (CAR) construct. The CAR construct can contain an anti-CD20 binding domain or anti-B cell maturation antigen (BCMA) binding domain, a CD8 hinge and transmembrane domain, a costimulatory domain, a CD3 ζ signalling domain, a combination thereof, or all thereof. The CAR construct can contain a domain encoding for a secreted common gamma chain cytokine such as a sIL 15 domain.

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

Hematopoeitic stem/progenitor cells (HSPC) and/or non-T effector cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to activate, promote proliferation of, detect, enrich, isolate, track, deplete and/or eliminate modified cells. The cells can also be modified to express a binding domain.

Provided are a BCMA-targeting engineered immune cell and the use thereof. In particular, a CAR specifically targeting BCMA is provided. In the CAR, an antigen binding domain contained therein is a J-derived scFv, having an antibody heavy-chain variable region shown in SEQ ID NO: 9, and an antibody light-chain variable region shown in SEQ ID NO: 10. Also provided are a CAR-T cell containing the CAR, and a duplex CAR and CAR T cells containing the J-derived scFv, and related uses thereof. Compared with CAR-T cells constructed by using other scFvs, the CAR-T cells constructed by the present invention have higher killing effects and tumor clearance ability.

Combined therapy for treating multiple myeloma (MM), comprising (a) a population of genetically engineered T cells, which may express a chimeric antigen receptor (CAR) that binds B-cell maturation antigen (BCMA), and (b) an anti-CD38 antibody such as daratumumab or lenalidomide or a derivative thereof.

Combined therapy for treating multiple myeloma (MM), comprising (a) a population of genetically engineered T cells, which may express a chimeric antigen receptor (CAR) that binds B-cell maturation antigen (BCMA), and (b) an anti-CD38 antibody such as daratumumab or lenalidomide or a derivative thereof.