The present invention relates to a polypeptide encoding a SLAMF7-binding chimeric antigen receptor (CAR), a polynucleotide encoding the SLAMF7-binding CAR polypeptide, a recombinant immune cell (preferably recombinant lymphocyte, more preferably recombinant T cell) comprising the polynucleotide, a method for producing recombinant immune cells and a pharmaceutical composition comprising recombinant immune cells. The recombinant immune cells and the pharmaceutical composition of the present invention may be used in methods for treating cancer in a patient thereby providing an improved treatment regimen. The inventors of the present application demonstrated that SLAMF7 CAR T-cells prepared by Sleeping Beauty gene transfer confer superior anti-myeloma efficacy in vivo compared to SLAMF7 CAR T-cells prepared by lentiviral gene transfer. Hence, SLAMF7 CAR T-cells that are prepared by virus-free SB gene transfer possess greater anti-myeloma efficacy and therapeutic potential, which leads to significantly improved clinical activity, and significantly improved clinical outcome.

Provided a chimeric anti-drug antibody receptor (CADAR) specific for anti-drug-antibody-based B cell receptor (BCR), the anti-drug antibody is induced by a therapeutic anti-TNF-alpha monoclonal antibody. Also provided compositions comprising the CADAR, polynucleotides encoding the CADAR, vectors comprising a polynucleotide encoding the CADAR, engineered cells comprising the CADAR, and method using the same.

The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The present disclosure relates generally to the field of immuno-therapeutics, and particularly relates to novel chimeric polypeptides, e.g., chimeric antigen receptors (CARs) that include a transmembrane domain from CD28 and a hinge domain. In some cases, the hinge domain is capable of promoting dimerization of the CARs. The disclosure also provides compositions and methods useful for producing such molecules, as well as methods for the detection and treatment of health conditions, such as proliferative diseases (e.g., cancer).

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

Provided herein are gRNA comprising a targeting domain that targets CD38, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD38 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Compositions and methods for treating diseases associated with expression of cluster differentiation 33 (CD33) and/or cluster differentiation 5 (CD5) involve two chimeric antigen receptors (CARs) specific to CD33 and CD5 and T cells with CD33 and CD5 dual-CAR. Methods of administering a genetically modified T cell expressing the dual-CAR can be used for autologous and allogeneic treatment of T cell malignancies.

The present disclosure provides BCMA-targeted chimeric antigen receptors (CARs) as well as preparation methods and applications thereof. The CARs of the present disclosure targets BCMA-positive cells, and can be used for treating BCMA-positive B-cell lymphoma, multiple myeloma and plasma cell leukemia.

An engineered immune cell comprising a first functional exogenous receptor capable of binding and depleting natural killer (NK) cells, and a second functional exogenous receptor, wherein the engineered immune cell has reduced MHC I on cell surface.

Provided herein are chimeric transmembrane receptor polypeptides configured to oligomerize upon recognition of an extramembrane signal. The receptors include an extramembrane domain, a transmembrane domain, and an intramembrane domain configured to induce activation of one or more intramembrane signal pathways upon oligomerization of the receptor. The provided receptors are particularly useful for engineered cell therapies. Also provided are systems and host cells including the disclosed receptors, and methods for using the disclosed materials.