Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: The present invention provides gene edited modified immune cells suitable for adoptive T cell therapy comprising a nucleic acid capable of downregulating CD3?, CD3?, CD3?, 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.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

Abstract: The present invention provides a method for preconditioning a subject who is about to receive a therapeutic T-cell composition, which comprises the step of administering one or more doses of a checkpoint inhibitor to the subject prior to administration of the therapeutic T-cell composition, wherein the subject does not receive any further doses of the checkpoint inhibitor after administration of the therapeutic T-cell composition.

Abstract: There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

Abstract: The present invention relates to the use of an IL-1? inhibitor for the prevention and/or treatment of neurotoxicity and/or cytokine release syndrome in a subject undergoing immunotherapy, wherein the IL-1? inhibitor is administered before immunotherapy.

Abstract: The present invention provides a cell which expresses a chimeric antigen receptor (CAR) or an engineered T-cell receptor (TCR), the cell comprising a nucleotide sequence of interest (NOI) which is selectively expressed by the cell depending on: i) the differentiation/exhaustion state of the cell; or ii) the presence of an environmental metabolite in the microenvironment of the cell.

Abstract: The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to an intracellular ligand which is released from a cell as a result of necrosis; and (ii) a cytokine receptor endodomain.

Abstract: The present invention provides a cell comprising first and second chimeric antigen receptors (CARs), which bind to different antigens, wherein the first CAR binds to Transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). The present invention also provides a cell comprising a tan CAR comprising first and second antigen-binding domains which bind to different antigens, wherein the first antigen binding domain binds the antigen Transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). The present invention further provides corresponding nucleic acid sequences and/or constructs, kits and vectors comprising said nucleic acid sequences and/or constructs, molecules and methods for making such cells. The cells may be used in cellular immunotherapy approaches for treating diseases such as multiple myeloma.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.