Abstract: The present invention provides a chimeric receptor which comprises: a ligand-binding exodomain; and an endodomain which comprises: (i) a cytokine receptor endodomain; and (ii) an intracellular T cell signalling domain.

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 provides a cell which expresses: (i) an intracellular single domain protein binder which binds a target protein and modulates an intracellular signalling pathway; and (ii) a chimeric antigen receptor (CAR) or a transgenic T cell receptor (TCR).

Abstract: The present invention provides a chimeric antigen receptor (CAR) which binds human CD22, having an antigen-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—NYWIH (SEQ ID No. 1); CDR2—GINPGNNYATYRRKFQG (SEQ ID No. 2) CDR3—EGYGNYGAWFAY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—RSSQSLANSYGNTFLS (SEQ ID No. 4); CDR2—GISNRFS (SEQ ID No. 5) CDR3—LQGTHQPYT (SEQ ID No. 6). The present invention also provides a cell comprising such a CAR and the use of such a cell to treat cancer.

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 relates to a cell which comprises a chimeric antigen receptor (CAR) or transgenic T cell receptor (TCR) and secretes an antibody which binds a transforming growth factor beta receptor (T?R).

Abstract: The present invention provides a kit of vectors comprising: (i) a first vector comprising a nucleic acid sequence encoding a first marker component; and (ii) a second vector comprising a nucleic acid sequence encoding a second marker component, wherein, when a cell is transduced with both the first and second vectors, the first and second marker components are expressed by the cell and associate forming a hetero-multimeric marker which is recognised by a cell sorting reagent whereas, when a cell is transduced with either the first or second vector alone, expression of the first or second marker component alone is not recognised by the cell sorting reagent.

Abstract: The present invention provides a chimeric antigen-receptor (CAR)-forming polypeptide comprising: (i) an antigen-binding domain; (ii) a coiled-coil spacer domain; (iii) a transmembrane domain; and (iv) an endodomain. The invention also provides a multimeric CAR formed by association of a plurality of CAR-forming polypeptides by virtue of association of their coiled-coil spacer domains.

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: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, and wherein each of the first and second CARs is an activating CAR comprising an activating endodomain.

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 a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, wherein the spacer of the first CAR is different to the spacer of the second CAR and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain.

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 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: 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 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 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 provides a chimeric antigen receptor (CAR) signalling system comprising; (i) a receptor component comprising an antigen binding domain, a transmembrane domain and a first binding domain; and (ii) an intracellular signalling component comprising a signalling domain and a second binding domain which specifically binds the first binding domain of the receptor component; wherein, binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain, whereas in the presence of the agent the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

Abstract: The present invention relates to engineered a cytolytic immune cell comprising: i) a releasable protein which comprises a polypeptide of interest (POI) and a first interaction domain; and ii) a retention protein which is retained within an intracellular compartment of the cell and comprises a second interaction domain which binds to the first protein interaction domain, wherein binding between the first protein interaction domain and second protein interaction domain is disrupted by the presence of an agent, such that in the absence of the agent, the first protein interaction domain and second protein interaction domain bind and result in retention of the POI within an intracellular compartment; whereas in the presence of the agent, the first protein interaction domain and second protein interaction do not bind and the POI is released from the intracellular compartment and expressed at the cell surface or secreted by the cell.

Abstract: The invention relates to a polypeptide comprising (i) an antigen binding domain (ii) a pre-T-alpha domain ectodomain; and (iii) a trans-membrane domain. The invention also relates to nucleic acids, kits, cells, methods and uses.

Abstract: The present invention provides a chimeric receptor which binds a target antigen on a target cell, which comprises: a first antigen binding domain which binds a first epitope of the target antigen, a second antigen binding domain which binds a second epitope of the target antigen; a transmembrane domain; and an intracellular signalling domain.