Provided herein are engineered T cells, expressing a chimeric receptor comprising an antigen-binding domain fused to an endogenous invariant CD3 chain of the immunoglobulin superfamily (invariant CD3-IgSF). In some embodiments, the engineered T cells contain a modified invariant CD3-IgSF chain locus that encodes the chimeric receptor. Also provided are cell compositions containing the engineered T cells, nucleic acids for engineering cells, and methods, kits and articles of manufacture for producing the engineered cells, such as by targeting a transgene encoding a portion of a chimeric receptor for integration into an invariant CD3-IgSF chain genomic locus. In some embodiments, the engineered cells, e.g. T cells, can be used in connection with cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered cells.

The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.

The present invention relates to antibodies, binding polypeptides, and scFvs specific for fibroblast activation protein (FAP) capable of cross reacting with canine, mouse, and human FAP.

The disclosure relates to immune cells comprising systems of two engineered receptors each having a ligand binding domain, collectively designed to target cells identified by loss of heterozygosity and used to treat a disease or disorder, for example, cancer. The disclosure provides immune cells expressing two engineered receptors, methods of making same, and polynucleotides and vectors encoding same.

The invention relates to nucleic acid constructs comprising a combination of a first sequence encoding a CAR and second sequence encoding an amino acid transporter, and to cells comprising such nucleic acid constructs. It also relates to methods of manufacturing said cells, and to pharmaceutical compositions comprising said nucleic acid constructs or cells, for use in the treatment of diseases with cellular amino-acid depletion such as cancer.

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.

The present application relates to functionally improved third generation BCMA-CARs comprising modified intracellular co-stimulatory domains, which can be used in adoptive cell therapy, e.g., in treatment of diseases and disorders such as cancer.

Provided is a chimeric antigen receptor, comprising a ligand-binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain. The co-stimulatory domain comprises an intracellular region of an NK-activated receptor or a ligand thereof. Also provided are an engineered immune cell comprising the chimeric antigen receptor and a use thereof in treatment of diseases, such as cancers, autoimmune diseases, and infections.

The invention relates to agents and methods for targeted delivery of payloads to cells. The agents and methods are useful for delivering therapeutic or diagnostic agents to target cells. In one embodiment, the invention involves administering RNA encoding a peptide or polypeptide (docketing compound) comprising a binding moiety (primary targeting moiety) binding to target cells and a further binding moiety (secondary target) binding to an agent that comprises a payload (effector probe). Following expression of the RNA, the primary targeting moiety may bind to a target antigen such as a cancer antigen on cancer cells and then a secondary targeting moiety comprised in the effector probe may target the secondary target to thereby precisely deliver a payload to the target cells such as cancer cells.

Provided is an engineered immune cell. The engineered immune cell expresses (i) a chimeric receptor, and (ii) exogenous CCL3, CCL4 and/or CCL5, has improved tumor killing activity, and can be used to treat cancer, infection or autoimmune diseases.