Monoclonal antibodies specific for mutated E-Cadherin peptide sequences

摘要

A novel monoclonal antibody recognises one or more of the following mutated (through deletion or point mutation) E-cadherin sequences: PGLRRQKRDW/IKSNKDKEGK (563del63); QGADTPPVGV/ERETGWLKVT (706del9); LSQDPELPDK/NRNTGVISVV (1036del15); SVVTTGLDRE/YKGQVPENEA (1103del129); DNPPIFNPTT/GLDFEAKQQY (1232del183); NNDGILKTAK/VSLTTSTATV (1414del69); TAVITVTDTNANPPIFNPTT (Asp370Ala); EVSLTTSTATDTVDVLDVNE (Val473Asp); EVSLTTSTATDTVDVLDVNE (Arg598Gln); AVSSNGNAVEE/ILITVTDQN (826del19). "/" shows the position of a deletion. Also claimed are: (1) a cell line producing the antibody of (1); (2) a therapeutic or diagnostic agent comprising at least one nucleic acid that hybridises under stringent conditions to at least a portion of a DNA sequence encoding one of the above mutated E-cadherin sequences, or the complementary strand or RNA transcript of such a DNA sequence, provided that the portion embraces the mutation, where the DNA sequence is selected from: CCT GGC CTC AGA AGA CAG AAG AGA GAC TGG/ATC AAA TCC AAC AAAGACAAAGAAGGCAAG (563del63); CAA GGA GCT GAC ACA CCC CCT GTT GGT GT/T GAA AGA GAA ACA GGA TGG CTG AAG GTG ACA (706del9); CTC AGC CAA GAT CCT GAG CTC CCT GAC AAA / AAC AGG AAC ACA GGA GTC ATC AGT GTG GTC (1036del15); AGT GTG GTC ACC ACT GGG CTG GAC CGA GAG / TAC AAG GGT CAG GTG CCT GAG AAC GAG GCT (1103del129); GAT AAT CCT CCG ATC TTC AAT CCC ACC ACG / GGC TTG GAT TTT GAG GCC AAG CAG CAG TAC (1232del183); AAC AAC GAT GGC ATT TTG AAA ACA GCA AAG / TCT CTC ACC ACC TCC ACA GCC ACC GTC (1414del69); ACA GCT GTG ATC ACA GTC ACT GAC ACC AAC GCT AAT CCT CCG ATC TTC AAT CCC ACC ACG (Asp370Ala); GAG GTC TCT CTC ACC ACC TCC ACA GCC ACC GAC ACC GTG GAT GTG CTG GAT GTG AAT GAA (Va1473AsP); GTG AAT GAC AAC GCC CCC ATA CCA GAA CCT CAA ACT ATA TTC TTC TGT GAG AGG AAT CCA (Arg598Gln); GCT GTG TCA TCC AAC GGG AAT GCA GTT GAG GA / G ATT TTG ATC ACG GTA ACC GAT CAG AAT (826del9); (3) DNA oligonucleotides encoding the amino acid sequences of (1); and (4) oligopeptides comprising the amino acid sequences of mutated E-cadherin as above.