A chimeric antigen receptor, containing a ligand binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain, the co-stimulatory domain containing CD94 and/or LTβ intracellular regions. The present invention further relates to engineered immune cells containing such a chimeric antigen receptor, and uses thereof in the treatment of diseases, such as cancer, autoimmune diseases, and infections.

The present invention discloses a nucleic acid molecule for encoding a chimeric antigen receptor targeting CD22 and CD19. The chimeric antigen receptor of the present invention can be used for treatment of CD19.sup.+ and CD22.sup.+ B-cell hematological tumors, as well as combined treatment with CD19 CAR-T cells or CD22 CAR-T cells.

The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) comprising a binding domain which binds a first epitope of a tumour antigen; and a polynucleotide which encodes a bi-specific protein which comprises a first binding domain which binds a second epitope of said tumour antigen; and a second binding domain which binds a cell surface antigen. The present invention also provides CAR systems, nucleic acids, vectors, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

Provided is an engineered immune cell. The expressions of at least one MHC related gene and at least one NK activating receptor binding molecule are suppressed or silenced, so as to suppress the killing of the engineered immune cell by NK cells. Also provided are a pharmaceutical composition comprising the engineered immune cell and use of the engineered immune cell in preparation of drugs for treatment of cancer, infection, or autoimmune diseases.

Provided is a bispecific chimeric antigen receptor targeting CD19 and CD22, which comprises extracellular antigen binding domains of heavy-chain variable regions and light-chain variable regions of anti-CD19 and anti-CD22 antibodies. Further provided is a bispecific CAR-T cell targeting CD19 and CD22.

The disclosure relates to methods of diagnosis and prognosis, compositions for immunotherapies, methods of improving said compositions, and immunotherapies using the same (e.g., T cells, non-T cells, TCR-based therapies, CAR-based therapies, bispecific T-cell engagers (BiTEs), and/or immune checkpoint blockade).

The present disclosure relates in some aspects to chimeric signaling receptors containing an extracellular domain capable of binding a molecule, such as an immunosuppressive cytokine, and a MyD88-containing intracellular domain capable of engaging a signaling pathway to activate an immune cell. In some aspects, the disclosure further relates to engineered cells, such as T cells, and compositions comprising the chimeric signaling receptors or engineered cells, and methods and uses thereof. In some embodiments, the cells may further express a genetically engineered recombinant antigen receptor directed against an antigen, such as a chimeric antigen receptor (CAR) or recombinant T cell receptor (TCR) and, in some cases, secrete a recombinant molecule, for example, a bispecific antibody.

Provided are a technique for preparing universal humanised CAR19-DNT cells and an application therefor. Specifically provided are universal CAR-T cells targeting CD19, the universal CAR-T cells expressing an exogenous CAR construct, and the CAR construct having the structure shown in formula I: L-scFv-H-TM-C-CD3ζ (formula I); in the formula, L is nothing or a signal peptide sequence; scFv is an antibody single-chain fragment variable region sequence targeting CD19; H is nothing or a hinge area; TM is a transmembrane domain; C is a costimulatory signal molecule; and CD3ζ is a cytoplasmic signal conduction sequence derived from CD3ζ. The provided universal humanised CAR19-DNT cells have the advantages of low immunogenicity, not requiring gene editing to avoid GvHD, high safety, high specificity, and obvious tumour killing effects, and the provided construction method can be implemented in large-scale production, the production costs being low.

A chimeric antigen receptor containing a CD3ε intracellular region with a Y/F mutation, includes an extracellular domain, a transmembrane domain, and an intracellular domain which are connected in sequence, where one end of the intracellular domain, which is connected to the transmembrane domain, is connected to the CD3ε intracellular region with the Y/F mutation, and the CD3ε intracellular region with the Y/F mutation refers to a Y/F mutant CD3ε intracellular region in which both tyrosines are mutated to phenylalanines in the ITAM of the CD3ε intracellular region. T cells modified with the chimeric antigen receptor have improved viability, decreased apoptosis level, and increased proliferation ability, and down-regulate the expression levels of cytokines IFN-γ and TNF-α.

The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.