The present invention provides an engineered immune cell targeting BCMA and use thereof. In particular, the present invention provides a CAR specifically targeting BCMA, the CAR comprising an antigen-binding domain which is an S-derived scFv, an antibody heavy chain variable region as shown in SEQ ID NO: 9 and an antibody light chain variable region as shown in SEQ ID NO: 10. The present invention also provides a CAR-T cell comprising the CAR, a double CAR- and CAR-T cell comprising the S-derived scFv, and related use thereof. Compared to CAR-T cells constructed using other scFvs, the constructed CAR-T cell of the present invention has a better killing effect and tumor elimination capability.

The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Provided are chimeric antigen receptors (CARs) having antigen specificity for B-cell Maturation Antigen (BCMA). Also provided are related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs. Methods of treating or preventing cancer in a mammal are also provided.

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.

Compositions, methods, expression vectors and engineered immune cells for improving therapies that entail the administration of allogeneic cells to a patient. An immune cell, e.g., a T cell, modified to comprise and/or express FasL protein or a FasL protein derivative from, for example, an expression vector comprising a polynucleotide that encodes FasL protein or a FasL protein derivative, and to express FasR at a reduced level, and further modified to comprise and/or express an antigen binding protein e.g., a chimeric antigen receptor (CAR). An improved method of CAR T-cell therapy that comprises administering the improved immune cells, and compositions that comprise the improved immune cells. Methods of improving persistence of administered cells and reducing activation-induced cell death comprising administering the improved cells.

The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells and/or CD8+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for pooling enriched CD4+ and CD8+ cells, such as at a 1:1 ratio, and then incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and/or cultivating the cells under conditions that promote proliferation and/or expansion. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.

The present disclosure provides processes for genetically engineering T cells, such as primary CD4+ T cells and/or CD8+ T cells, for use in cell therapy that does not involve expanding the cells. In particular aspects, the provided processes successfully generate compositions of engineered T cells, such as containing populations of engineered T cells, that express a chimeric antigen receptor (CAR) within a shortened amount of time as compared to alternative engineering processes, such as processes that involve expanding the cells. In certain aspects, the provided processes successfully generate a composition of engineered T cells suitable for use in cell therapy within 4 days from when the process to stimulate or activate the cells is initiated. In some aspects, the resulting engineered cell compositions are composed of cell population that are less differentiated, less exhausted, and more potent than engineered T cell compositions generated by other means, such as by processes that involve expanding the cells. Also provided are compositions of T cells generated by the provided methods and their uses for treating subjects.

The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

Provided herein are activated adoptive T-cell compositions targeting plasma cell dyscrasias such as multiple myeloma and methods of treating plasma cell dyscrasias such as multiple myeloma using such compositions. The T-cell compositions of the present disclosure are activated against a select group of antigens associated with multiple myeloma (MMAAs) and, in certain embodiments, in combination with more widely expressed tumor associated antigens (TAAs). In particular, the T-cell compositions of the present disclosure are directed to the MMAAs selected from B-cell maturation antigen (BCMA), X box Protein 1 (XBP1), CS1, and Syndecan-1 (CD138), or a combination thereof. In certain embodiments, the T-cell composition includes T-cells activated to a TAA selected from preferentially expressed antigen of melanoma (PRAME), Survivin, Wilms' Tumor 1 protein (WT1), and melanoma antigen 3 (MAGE-A3), or a combination thereof.

Provided herein is a serum-free media for culturing, such as cultivating, preparing and/or producing cells, such as immune cells, such as genetically engineered cells. Also provided is a liquid basal media and frozen supplements that can be used to produce serum-free media. The provided embodiments include methods for producing serum-free media and methods for culturing cells, such as activating, transducing, cultivating or expanded cells, in the presence of serum-free media.