Disclosed herein are methods for treatment of a mesothelin (MSLN)-expressing cancer in a human subject comprising administration of, e.g., a plurality of anti-MSLN T cell receptor fusion protein (TFP)-expressing T cells. A ratio of CD4+ to CD8+ T cells in a sample from the human subject may have been determined before the administration of the plurality of anti-MSLN TFP-expressing T cells. The plurality of anti-MSLN TFP-expressing T cells may comprise a pre-determined ratio of CD4+ to CD8+ T cells.

The disclosure provides immune cells comprising a first activator receptor specific to mesothelin and a second inhibitory receptor specific to a ligand that has been lost in a mesothelin-positive cancer cell, and methods of making and using same for the treatment of cancer.

Provided are a CD22-targeted chimeric antigen receptor, a preparation method therefor and an application thereof. The chimeric antigen receptor comprises a leader sequence, a CD22-targeted scFv, a hinge region, a transmembrane region, and an intracellular signal domain. Provided are a nucleic acid molecule encoding the chimeric antigen receptor and a corresponding expression vector, a CAR-T cell, and an application thereof. The chimeric antigen receptor targets CD22 positive cells and can be used for treating CD22-positive B-cell leukemia, and some CD19-negative and CD22-positive patients in which acute B-cell leukemia has recurred after anti-CD19 CAR-T treatment.

An engineered immune cell, which expresses (i) a cell surface molecule that specifically recognizes a ligand, (ii) an exogenous interleukin, and (iii) an exogenous Flt3L, XCL2, and/or XCL1; the engineered immune cell can be used for treating cancer, infection, or autoimmune diseases; and compared with a traditional engineered immune cell, the engineered immune cell has significantly improved tumor killing activity.

The present disclosure relates to a system for immune therapy, the system comprising a sample processing module configured to obtain whole blood from a subject; a cell incubation module configured to activate blood cells of the whole blood and/or introduce a vector into the blood cells of the whole blood; and a cell infusion module configured to infuse at least a portion of the whole blood to the subject, wherein the blood cells comprise CD3+ cells, NK cells, myeloid cells, and neutrophils.

The present invention provides gene edited modified immune cells suitable for adoptive T cell therapy comprising a nucleic acid capable of downregulating CD3δ, CD3ε, CD3γ, B2M, CIITA, TAP1, TAP2, TAPBP, NLRC5, HLA-DM, RFX5, RFXANK, RFXAP, and invariant chain; and further comprising an exogenous nucleic acid encoding a chimeric antigen receptor (CAR), an engineered T cell receptor (TCR), a Killer cell immunoglobulin-like receptor (KIR), dominant negative receptor and/or a switch receptor. Also provided are compositions and methods for generating the modified immune cell, and methods of using the modified immune cells for adoptive therapy and treating a disease or condition.

The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).

Aspects of the present disclosure provide methods for treating a subject having a carcinoembryonic antigen (CEA)-positive tumor using a conditioning regimen (lymphodepleting treatment), which comprises administering one or more doses of a lymphodepleting agent to a subject, and a treatment regimen, which comprises administrating one or more doses of the anti-CEA CAR T cells and/or the ICK proteins to the subject.

Anti-BCMA antibodies and chimeric antigen receptors (CARs) are provided. Immune cells expressing the anti-BCMA CAR can be used to treat cancer. The anti-BCMA antibodies and CARs can recognize the extracellular domains of human BCMA. The anti-BCMA CAR T cells show specific cytotoxicity towards BCMA-positive target cells.

The present disclosure provides methods of preparing immune cells, e.g., T cells and/or NK cells, comprising contacting the cells with programmable cell-signaling scaffolds in a medium comprising at least about 5 mM potassium ion. In some aspects, the methods disclosed herein increase 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 (CAR) or an engineered T cell receptor (TCR). In some aspects, the cells are administered to a subject in need thereof.