摘要:
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.
摘要:
A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identificaton of high affinity TCRs. Several high affinities are disclosed.
摘要:
The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all for part of a TCR α chain, except the transmembrane domain thereof, and (ii) all or part of a TCR β 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.
摘要:
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 Cl-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 -0-, -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; -NR8R8wherein each R8 may be the same or different, or form a ring when taken together with the nitrogen to which they are attached; an ester group; or an optionally substituted aryl, aryloxy, cycloalkyl, cycloalkenyl or heterocyclic group; and R7 represents H or C1-C6 alkyl; or when taken together with the atom or atoms to which they are attached R6 and R7 form a monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula -(Z)n-(Alk)- or -(Alk)-(Z)n- wherein Z represents -0-, -S- or -NH-, Alk is as defined in relation to R6 and n is 0 or 1.
摘要:
The present invention provides a superantigen quality control assay, particularly for SEA-E120, comprising incubating a standard amount of a superantigen-containing test sample with a standard amount of a soluble TCR which binds the superantigen, separating unbound TCR from the resultant superantigen/ TCR-containing sample, quantifying the TCR bound in that sample, and comparing that result with a reference result characterising a control superantigen-containing sample. Also provided are soluble TCRs useful as reagents in said assay.
摘要:
The present invention provides a soluble bifunctional protein comprising an association between a T cell receptor and a superantigen. Also provided are therapeutic compositions comprising said bifunctional proteins and methods for the use thereof.
摘要:
N-(l-Aza-bicyclo[2.2.2]oct-3-yI)-4-(6,9-difluoro-3-oxo-1,3-dihydro-pyrazolo[4,3clcinnolin-2-yI)-benzamide is a CD80 antagonist, useful in the treatment of diseases which benefit from immuno-inhibition.
摘要:
The present invention provides gamma-delta T cell receptors (ϜδTCRs) with an introduced disulfide interchain bond. Such proteins, and cells expressing of such proteins on the surface thereof, have value in methods for distinguishing between cell populations by the TCR ligand they present, and in the treatment of diseases.
摘要:
The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC (SEQ ID NO:126) 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 peptide-HLA complex of less than or equal to 1 μM and/or have an off-rate (koff) of 1×10−3 S−1 or slower.
摘要:
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 and R10 form a ring when taken together with the nitrogen to which they are attached, which ring is optionally substituted; and R7 represents H or C1-C6 alkyl; or when taken together with the atom or atoms to which they are attached R6 and R7 form an optionally substituted monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula - (Z)n-(Alk)- or - (Alk)-(Z)n- wherein Z represents -O-, -S- or -NH-, Alk is as defined in relation to R6 and n is 0 or 1.