The present invention relates to a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) a chimeric TNF receptor (TNFR) which comprises (a) a binding domain which is capable of binding a TNFR ligand; and (b) a TNFR signalling domain.

This invention provides chimeric antigen receptors (CARs) targeting human EphA3 and dual targeting CARs that bind to human EphA3 and to human mutant epidermal growth factor receptor variant III (EGFRvIII). This invention also relates to CAR-T cells comprising the provided CARs or the dual targeting CARs. Methods for treating a solid tumor cancer by administering the CARs are provided.

The present disclosure provides improved genome editing compositions and methods for editing a casitas B-lineage (Cbl) lymphoma proto-oncogene B (CBLB) gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

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.

A programmable cell receptor complex expressed by an immunocyte, wherein the programmable receptor complex includes a plurality modified receptor subunits, wherein the modified receptor subunits have been engineered or modified to include FcRI receptor components, biotin-binding components, or both, and wherein the FcRI receptor components and biotin-binding components are operative to bind to target detector molecules that bind to or otherwise interact with predetermined targets.

In certain embodiments, this disclosure provides methods to generate DNA, RNA and/or DNA-peptide nanostructures based chimeric antigen receptor (CAR) T cell (engineered T cell) for cancer immunotherapy, and compositions made by these methods.

Non-natural sugars modified with a bioorthogonal reactive group are added into a culture medium of immune cells such as NK cells to obtain immune cells modified with the bioorthogonal reactive group; and then, under a physiological condition, a targeting ligand, for example, a nanobody, is modified to a surface of each of the immune cells through a bioorthogonal reaction, wherein the targeting ligand has one terminal with a bioorthogonal reactive pairing group which is capable of being matched and connected with the bioorthogonal reactive group to generate a connecting reaction, connection is implemented by a transpeptidase SrtA-mediated chemoenzymatic method. The targeting ligand highly specifically recognizes and binds to a highly expressed receptor on the surface of tumor cells. The immune cell modified with the targeting ligand can specifically bind in a targeted way to the tumor cells, therefore generating cytokines, killing and damaging tumor cells.

Engineered trimeric CD70 proteins for use in ex vivo T cell manufacturing are described. Use of the proteins during manufacturing creates expanded T cell populations with enhanced properties such as earlier proliferation in culture; selective expansion of nave and memory T cell subsets; longer persistence in vivo following administration to a subject; and improved therapeutic effect. Use of the proteins as therapeutics provide anti-cancer and anti-viral effects. The proteins can also be used as agonistic cell culture reagents in in vitro uses.

A truncated EGFR (tEGFR) cell surface molecule and its uses is provided herein. The tEGFR cell surface molecule includes an EGFR domain IV and does not include an EGFR domain III and may be used, inter alia, as an in vivo tracking marker for genetically modified human T cells. Furthermore, the tEGFR cell surface molecule has cellular depletion potential through mediated through specific anti-domain IV EGFR antibodies. Thus, the tEGFR cell surface molecules provided herein may, inter alia, be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential.

The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.