The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen CS1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen CS1. The alpha, beta and gamma polypeptides composing these CARs are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer, especially multiple myeloma.

Control Devices are disclosed including RNA destabilizing elements (RDE), and RNA control devices, combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. RDEs can be combined with RNA control devices to make RDEs that include ligand mediated control. These smart RDEs and other RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell.

The present invention provides a chimeric antigen receptor (CAR) comprising: an antigen binding domain specific for folate receptor 1 (FolR1), a spacer, a transmembrane domain and an intracellular signaling domain. Moreover it was found that an antigen binding domain that comprises from the N- to the C-terminus the heavy chain variable region of an antibody (VH) comprising the amino acid sequence Seq ID No:2 a light chain variable region of an antibody (VL) comprising the amino acid sequence Seq ID No:4 shows superior killing properties compared to other variants.

The present disclosure relates to Dsg2 binding molecules, nucleic acid molecules encoding the Dsg2 binding molecules and compositions comprising the same and methods of use thereof for treating or preventing cancer.

Described are modified T cells overexpressing one or more glucose transporters. Pharmaceutical compositions containing the glucose transporter overexpressing T cells are also described. The glucose transporter overexpressing T cells and pharmaceutical compositions can be used in adoptive cell therapies.

A method for detecting cells having granules expressing G protein coupled receptor-associated sorting protein 1 (GASP-1) or a fragment thereof is provided. The detection method may comprise: (a) contacting the cells with an effective amount of a binding protein, wherein the binding protein comprises an antigen binding fragment that specifically binds GASP-1; and (b) identifying cells having granules bound to the binding protein. The GASP-1 granules may be in the cytosol or on the surface of the cells. Also provided are methods for producing T-cells comprising a chimeric antigen receptor, anti-GASP-1 antibody or a bi-specific binding protein. Further provided are methods for treating GASP-1-mediated to disease or inactivating exosomes, microvesicles or oncosomes.

The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).

The invention relates to a dendritic cell (DC) vaccine for use in a method of treating cancer in a patient, wherein the patient is selected for treatment with said DC vaccine. The selection inter alia comprises determining in a tumor sample from the patient the amount of CD8+ T-cells and/or the tumor mutation burden (TMB) and comparing the determined amount to a predetermined threshold level. The selection allows identifying patients that particularly benefit from DC treatment.

Disclosed are methods of eliminating at least one target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).

The preset disclosure provides methods of culturing cells, e.g., pluripotent cells, multipotent cells, and/or immune cells (e.g., T cells and/or NK cells) in a medium comprising at least about 5 mM potassium ion, wherein the medium is not hypertonic. In some aspects, the medium is hypotonic. In some aspects, the methods disclosed herein increases the number of less-differentiated cells in the population of cells. In some aspects, the cultured cells are engineered, e.g., to comprise a chimeric antigen receptor or an engineered T cell receptor. In some aspects, the cells are administered to a subject in need thereof.