Provided herein are targeted cytokine constructs and method of engineered cell therapy by administering a targeted cytokine construct in combination with an engineered cell therapy, for use in treating a disease, e.g., a proliferative disease, e.g., a cancer.

Provided herein are engineered immune cells and populations thereof for administration to subjects to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of CD48, CD58, ICAM-1, RFX5, NLRC5, TAP2, 2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) and/or a CD70 binding protein to target tumor cells or other damaged cells in the subject and/or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

The present invention relates to gamma delta (??) T cells and/or Natural Killer (NK) cells expressing constructs to provide for the expression of a Chimeric Antigen Receptor (CAR) incorporating the signalling domain of FCY Receptors. Suitably the invention also relates to constructs to provide such CARs and methods for introducing such CARs into cells and expressing such CARs in cells comprising receptors of gamma delta (??) T cells and/or Natural Killer (NK) cells.

The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) off-the-shelf T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.

Methods and compositions for treating cancer, particularly improved CAR-T methods, are disclosed.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Chimeric antigen receptors containing human CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.