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 invention relates to a method of determining the T cell receptor ? chain (TRBC) gene type of a cell, the method comprising (a) determining the J gene type expressed in said cell, and (b) inferring from (a) the TRBC gene type expressed in said cell. The invention further relates to use of a CAR T cell targeted to a T cell receptor ? chain (TRBC) type 1, or a CAR T cell targeted to a T cell receptor ? chain (TRBC) type 2. The invention further relates to a method of medical treatment, and to nucleic acid probes.

Abstract: The present invention provides a chimeric antigen receptor (CAR) which specifically binds CD79 as well as a nucleic acid sequence and a vector encoding the CAR. It further provides a cell which expresses the CAR at the cell surface.

Abstract: The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

Abstract: The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

Abstract: The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extracellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.

Abstract: There is provided a plasmid system for transfection into a cell to create a producer cell, the system comprising: a. a helper plasmid comprising a first nucleotide sequence encoding Murine leukemia virus (MLV)-derived Gag and Pol poly-proteins; b. an envelope plasmid comprising a second nucleotide sequence encoding an Env protein; c. a genome plasmid comprising a third nucleotide sequence encoding a retroviral genome, wherein the first nucleotide sequence is codon-shuffled to remove any significant regions of homology with the third nucleotide sequence; and wherein the second nucleotide sequence is codon-optimised for expression in the producer cell.

Abstract: The present invention provides a nucleic acid construct comprising: a first nucleotide sequence of interest (NOI1); a frame-slip motif or a translational readthrough motif (FSM/TRM); and a second nucleotide sequence of interest (NOI2). The invention also provides vectors and cells expressing such a construct. The invention also provides a method for modulating the relative expression of two transgenes in a nucleic acid construct which comprises the step of including a frame-slip motif or a translational readthrough motif between the two transgenes in order to reduce the expression of the downstream transgene.

Abstract: The present invention provides antibodies and polyclonal antibody preparations which bind the intracellular portion of either T-cell receptor constant region 2 (TRBC2) or T-cell receptor constant region 1 (TRBC1). The antibodies can be used to determine whether a T-cell malignancy clonally expresses TRBC1 or TRBC2.

Abstract: The present invention provides a method of preparing a population of genetically modified cells which comprise a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR) comprising: providing a starting population of cells; depleting said starting population of cells which express a target antigen; and introducing into a cell in the depleted starting population a nucleic acid sequence which encodes a CAR or transgenic TCR against the target antigen. The present invention also provides genetically modified cells, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TOR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: Provision of a chimeric antigen receptor (CAR) comprising a disialoganglioside (GD2)-binding domain which comprises •a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: •b) a light chain variable region (VL) having CDRs with the following sequences: T cells expressing such a CAR are useful in the treatment of some cancers.

Abstract: The present invention provides a kit of vectors for transducing an immune cell with multiple transgenes comprising: (i) a first vector which comprises a first transgene and a nucleotide sequence encoding a transcription factor and; and (ii) a second vector which comprises a second transgene wherein expression of the second transgene within a host cell is dependent upon expression of the transcription factor.

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

Abstract: The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

Abstract: The present invention provides a chimeric polypeptide comprising: an antigen-binding domain which constitutively binds to an ectodomain of a first chain of a cytokine receptor; a transmembrane domain; and an endodomain from a second chain of the cytokine receptor which chimeric polypeptide, when expressed in a cell, binds to the endogenous first chain of the cytokine receptor causing constitutive cytokine signalling.