Abstract: The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a KD for the said that peptide-HLA complex of less than or equal to 1 ?M and/or have an off-rate (koff) of 1×10?3 S?1 or slower.

Abstract: The present invention provides T cell receptors (TCRs) having the property of binding to ILAKFLHWL-HLA-A*0201 and comprising at least one TCR ? chain variable domain and/or at least one TCR ? chain variable domain CHARACTERISED IN THAT said TCR has a KD for the said ILAKFLHWL-HLA-A*0201 complex of less than or equal to 1 ?M and/or has an off-rate (koff) for the ILAKFLHWL-HLA-A*0201 complex of 1×10?3 S?1 or slower.

Abstract: This invention provides a cell presenting at least one T cell receptor (TCR) anchored to the membrane by a transmembrane sequence, said TCR comprising an interchain disulfide bond between extracellular constant domain residues which is not present in native TCRs.

Abstract: N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-4-(6,9-difluoro-3-oxo-1,3-dihydro-pyrazolo[4,3-c]cinnolin-2-yl)-benzamide is a CD80 antagonist, useful in the treatment of dieases which benefit from immuno-inhibition.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR ? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: Compounds of formula (IA) or (IB) are inhibitors of CD80 and useful in immunomodulation therapy: wherein Ar represents an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group having from 5 to 10 ring atoms; R1 and R2 independently represent H, or C1-C6 alkyl; R3 represents H; F; CI; Br, —NO2; —CN; C1-C6 alkyl optionally substituted by F or CI; or C1-C6 alkoxy optionally substituted by F; R4 represents a carboxylic acid group (—COOH) or an ester thereof, or —C(?O)NR6R7, —NR7C(?O)R6, —NR7C(?O)OR6, —NHC(?O)NR7R6 or —NHC(?S)NR7R6 wherein R6 represents H, or a radical of formula -(Alk)m-Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C1-C12 alkylene, or C2-C12 alkenylene, or C2-C12 alkynylene radical or a divalent C3-C12 carbocyclic radical, any of which radicals may be interrupted by one or more —O—, —S— or —N(R8)— radicals wherein R8 represents H or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, or C3-C6 cycloalkyl, and Q represents H; —CF3; —OH; —SH; —

Abstract: This invention is directed to a method for inhibiting cytotoxic T lymphocyte (CTL) activity in which soluble CD8 is used as the inhibitor. The invention is further directed to soluble forms of the CD8 molecule which can be administered to a patient. The method of this invention is particularly useful for immunosuppressive therapy in which inhibition of CTL activity is desirable, for example, in patients undergoing transplantation.

Abstract: Compounds of formula (I) are inhibitors of CD80 and useful in immunomodulation therapy: wherein R1 and R3 independently represent H; F; CI; Br; —NO2; —CN; C1-C6 alkyl optionally substituted by F or Cl; or C1-C6 alkoxy optionally substituted by F; R4 represents a carboxylic acid group (—COOH) or an ester thereof, or —C(?O)NR6R7, —NR7C(?O)R6, —NR7C(?O)OR6, —NHC(?O)NR7R6 or —NHC(?S)NR7R6 wherein R6 represents H, or a radical of formula -(Alk)m-Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C1-C12 alkylene, or C2-C12 alkenylene, or C2-C12 alkynylene radical or a divalent C3-C12 carbocyclic radical, any of which radicals may contain one or more —O—, —S— or —N(R8)— links wherein R8, represents H or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, or C3-C6 cycloalkyl, and Q represents H; —NR9R10 wherein R9 and R10 independently represents H; C1-C4 alkyl; C3-C4 alkenyl; C3-C4 alkynyl; C3-C6 cycloalkyl; an ester group; an optionally substituted carbocyclic or heterocyclic group; or R9

Abstract: The present invention provides a multimers of class I Major Histocompatibility Complexes (MHCs) having a modified P2-microglobulin whose binding to CD8 is inhibited. Such MHCs are capable of inhibiting CD8+ T cell response, particularly by inducing apoptosis or anergy of the T cell. The invention also provides nucleic acids encoding such molecules, and the use of such multimers and nucleic acids in immunosuppressive therapy, in particular as inhibitors of cytotoxic T cell responses.

Abstract: A single chain T cell receptor (scTCR) comprising an a segment constituted by a TCR ? chain variable region sequence fused to the N terminus of a TCR ? chain constant region extracellular sequence, a ? segment constituted by a TCR ? chain variable region fused to the N terminus of a TCR ? chain constant region extracellular sequence, and a linker sequence linking the C terminus of the a segment to the N terminus of the ? segment, or vice versa, the constant region extracellular sequences of the ? and ? segments being linked by a disulfide bond, the length of the linker sequence and the position of the disulfide bond being such that the variable region sequences of the ? and ? segments are mutually orientated substantially as in native ?? T cell receptors. Complexes of two or more such scTCRs, and use of the scTCRs in therapy and in various screening applications are also disclosed.

Abstract: The present invention relates to a synthetic multivalent T cell receptor complex for binding to a MHC-peptide complex, which multivalent T cell receptor complex comprises a plurality of T cell receptors specific for the MHC-peptide complex. It is preferred that the T cell receptors are refolded recombinant soluble T cell receptors. The synthetic multivalent T cell receptor complex can be used for delivering therapeutic agents or for detecting MHC-peptide complexes, and methods for such uses are also provided.

Abstract: The present invention relates to a recombinant soluble T cell receptor. The T cell receptor (TCR) is refolded and comprises a recombinant TCR ? or ? chain extracellular domain having a first heterologous C-terminal dimerization peptide; and a recombinant TCR ? or ? chain extracellular domain having a second C-terminal dimerization peptide which is specifically heterodimerized with the first dimerization peptide to form a heterodimerization domain, which may be a coiled coil domain. The invention also provides nucleic acid sequences encoding the recombinant TCR and a method for producing the recombinant TCR. The TCR may be labelled with a detectable label so as to enable the detection of specific MHC-peptide complexes. Alternatively, it can be linked to a therapeutic agent such as a cytotoxic agent or an immunostimulating agent so as to deliver such an agent to the site of a specific MHC-peptide complex.

Abstract: The present invention provides a method of inhibiting the binding of a CD8+ T cell to a class I Major Histocompatibility Complex (MHC). The method comprises exposing the class I MHC to a modified &bgr;2-microglobulin whose binding to CD8 is inhibited. Also provided are modified &bgr;2-microglobulin molecules and nucleic acids encoding such molecules.

Abstract: The present invention provides methods for sequentially screening for compounds with the potential to interfere with low affinity receptor-ligand contacts using an interfacial optical assay, such as surface plasmon resonance (SPR). The method comprises contacting a candidate compound with an immobilized receptor, contacting the receptor, which may or may not have the candidate compound bound to it, with the ligand and detecting by interfacial optical assay whether or not the ligand or ligand-compound complex has bound to the receptor or receptor-compound complex. If the ligand binds, the method shows that the compound does not inhibit the receptor-ligand interaction. If the ligand does not bind, the method shows that the compound inhibits the receptor-ligand interaction. The method is particularly useful for screening for inhibitors of the interaction between MHC/peptide complex and T cell receptor, MHC/peptide complex and CD8 coreceptor or MHC/peptide complex and CD4 coreceptor.

Abstract: The present invention provides methods for sequentially screening for compounds with the potential to interfere with low affinity receptor-ligand contacts using an interfacial optical assay, such as surface plasmon resonance (SPR). The method comprises contacting a candidate compound with an immobilised receptor, contacting the receptor, which may or may not have the candidate compound bound to it, with the ligand and detecting by interfacial optical assay whether or not the ligand or ligand-compound complex has bound to the receptor or receptor-compound complex. If the ligand binds, the method shows that the compound does not inhibit the receptor-ligand interaction. If the ligand does not bind, the method shows that the compound inhibits the receptor-ligand interaction. The method is particularly usefull for screening for inhibitors of the interaction between MHC/peptide complex and T cell receptor, MHC/peptide complex and CD8 coreceptor or MHC/peptide complex and CD4 coreceptor.