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 provides a chimeric antigen receptor (CAR) comprising an antigen-binding domain with an affinity in the range of 50 nM to 500 nM, wherein said affinity comprises component kinetics such that the association rate constant (kon) is greater than or equal to 1×105 M?1 S?1, and/or the dissociation rate constant (koff) is greater than or equal to 0.01 s?1.

Abstract: The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

Abstract: The present disclosure provides a cell comprising: an anti-CD33 chimeric antigen receptor (CAR); an anti-CLL1 CAR; and an anti- CD123 and/or anti- CAR FLT3 CAR. The cell can be used in the treatment of a disease such as acute myeloid leukemia (AML).

Abstract: The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.

Abstract: The present invention provides polypeptides with coronavirus neutralising capacity.

Abstract: 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.

Abstract: The present invention provides a method for treating a solid cancer which comprises the step of administering a cell to a subject, wherein the cell comprises a nucleic acid sequence encoding interleukin 12 (IL-12) downstream of a frame-slip motif (FSM) or a translational readthrough motif (TRM).

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 cell which co-expresses a chimeric antigen receptor (CAR) and a dominant negative C-terminal Src kinase (dnCSK). The present invention also provides nucleic acid constructs, vectors and methods for making such a cell and the use of such a cell in the treatment of diseases such as cancer by adoptive immunotherapy.

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: There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

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 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.

Abstract: There is provided an effector immune cell which expresses a cell surface receptor or receptor complex which specifically binds an antigen recognition receptor of a target immune cell; which effector immune cell is engineered such that when a synapse is formed between the effector immune cell and the target immune cell, the capacity of the effector immune cell to kill the target immune cell is greater than the capacity of the target immune cell to kill the effector immune cell. There is also provided the use of such a cell in methods for treating cancer, preventing allograft rejection and GVHD.

Abstract: The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) a polypeptide capable of co-localizing a beta-2 microglobulin component of a MHC class I molecule with an intracellular signalling domain within the cell.

Abstract: The present invention provides a method for selecting for cells transduced to express a nucleic acid sequence of interest (NOI), which comprises the following steps: (a) transducing a population of cells with a vector co-expressing the NOI and a nucleic acid sequence which inhibits Fas expression or activity in the cell; (b) exposing the cells from (a) to FasL such that untransduced cells are eliminated by apoptosis. The present invention also provides a molecule which comprises a Fas-binding domain linked to an intracellular retention signal which may be used in such a method to inhibit Fas expression.

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 chemokinc and a cell-surface antigen; and (ii) a cytokine receptor cndodomain.

Abstract: The present invention relates to a cell which comprises; (a) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (b) a FasL-binding receptor (FLBR) comprising; (i) a Fas ectodomain and a TNFR endodomain, wherein the TNFR endodomain comprises the signalling portion of the decoy receptor 2 (DcR2), GITR, CD30, XEDAR, CD40, CD27, BCMA or Fn14 endodomain, or (ii) a membrane-bound decoy receptor 3 (DcR3).