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 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 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 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 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 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 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.

Abstract: The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR wherein the first CAR comprises an activating endodomain and the second CAR comprises an inhibitory endodomain, wherein the inhibitory endodomain comprises C-terminal Src Kinase (CSK).

Abstract: The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; and (isi) a membrane-tethered signal-dampening component (SDC) comprising a signai-dampening domain (SDD).

Abstract: The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; (ii) a membrane tethering component (MTC) which comprises a first dimerization domain; and (Hi) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specifically binds the first dimerisation domain of the membrane-tethering component. Dimerisation between the MTC and SDC may be controllable with an agent, meaning that the agent can be used to control CAR-mediated cell signalling.

Abstract: The present invention relates to a cell which coexpresses a first chimeric antigen receptor (CAR) and a second CAR, wherein the first CAR comprises a phosphorylation amplifying endodomain and wherein the second CAR comprises 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, a transmembrane domain and an intracellular 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; and wherein the first and/or second CAR is a tunable CAR having an intracellular domain comprising a heterodimenzation domain, which intracellular domain is capable of binding a separate intracellular signalling molecule which comprises a reciprocal heterodimenzation domain and a signalling domain.

Abstract: The present invention provides signal transduction modifying protein which comprises a domain which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (pITIM). The signal transduction modifying protein lacks a functional phosphatase domain. The present invention also provides cells which express such a signal transduction modifying protein, and cells which co-express such a signal transduction modifying protein together with a chimeric antigen receptor (CAR).

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.