Monoclonal antibodies, antigens and diagnosis and therapy of malignant diseases

Abstract

The invention concerns novel DNA and amino acid sequences of monoclonal antibodies (mAbs) raised against lymphoblastoid cells and peptides to which the mAbs bind to. The invention also concerns diagnostic assays using said antibodies or peptides for detecting individuals with a high probability of having a malignant disease and, at times, for detecting an individual having a specific malignant disease. The invention further concerns pharmaceutical compositions comprising the mAbs or peptides of the invention for use in the treatment of various malignant diseases as well as methods for the treatment of malignant diseases using the mAbs or peptides of the invention.

1 . A monoclonal antibody comprising a heavy chain variable region having at least 70% identity to the amino acid sequence of FIG. 1; a light chain variable region having at least 70% identity to the amino acid sequence of FIG. 2; or both said heavy chain variable region and said light chain variable region.  
     
     
         2 . The monoclonal antibody according to  claim 1 , wherein said heavy chain variable region comprises of the amino acid sequence of FIG. 1; said light chain variable region comprises of the amino acid sequence of FIG. 2; or both said heavy chain variable region and said light chain variable region comprising FIG. 1 and FIG. 2 correspondingly.  
     
     
         3 . A monoclonal antibody, wherein said antibody binds to an antigen to which any one of the monoclonal antibodies of  claim 1  specifically bind.  
     
     
         4 . The antibody according to  claim 1 , wherein the antibody is a chimeric human-mouse antibody.  
     
     
         5 . A nucleic acid molecule encoding the amino acid sequence of the monoclonal antibody of  claim 1 .  
     
     
         6 . An expression vector having the nucleic acid sequence of  claim 5 .  
     
     
         7 . An expression vector according to  claim 6 , comprising of plasmid pKN110 or plasmid pG1D110.  
     
     
         8 . A cell transfected with the expression vector of  claim 6 .  
     
     
         9 . A hybridoma cell line producing at least one of the monoclonal antibodies of  claim 1 .  
     
     
         10 . A peptide having an amino acid sequence at least 85% identical to the amino acid sequence of the peptides in FIG. 10, FIG. 11, or FIG. 12.  
     
     
         11 . The peptide of  claim 10 , wherein the peptide comprises of the amino acid sequence of the peptide in FIG. 10, FIG. 11, or FIG. 12.  
     
     
         12 . A protein or peptide comprising one or more of the peptides of  claim 10 .  
     
     
         13 . A peptide analog of any of the peptides of  claim 10 , wherein said peptide analog has substantially the same level of binding to a monoclonal antibody comprising a heavy chain variable region having at least 70% identity to the amino acid sequence of FIG. 1, a light chain variable region having at least 70% identity to the amino acid sequence of FIG. 2, or both said heavy chain variable region and said light chain variable region.  
     
     
         14 . A method for identifying a tested individual with a high probability of having a malignant disease comprising: 
 (a) obtaining a body fluid sample from said individual;    (b) contacting said sample with at least one of the monoclonal antibodies of  claim 1 , or a monoclonal antibody, wherein said antibody binds to an antigen to which any one of the monoclonal antibodies of  claim 1  specifically bind;    (c) determining the extent of binding of said monoclonal antibody to T-cells within said sample; and    (d) comparing the extent of (c) to the extent of binding of the monoclonal to T-cells in a sample obtained from a healthy individual, wherein a significant difference between said extents of binding indicate that said tested individual has a high probability of having a malignant disease.    
     
     
         15 . The method according to  claim 14 , wherein before step (b) the peripheral blood mononuclear cells are separated, said separated the peripheral blood mononuclear cells are then contacted in step (c) with said monoclonal antibody.  
     
     
         16 . The method according to  claim 14 , wherein said body fluid is blood.  
     
     
         17 . The method according to  claim 14 , wherein the extent of binding of the monoclonal antibodies obtained from said tested individual is higher than the extent of binding of the same monoclonal antibody to T-cells of healthy individuals.  
     
     
         18 . The method according to  claim 17 , wherein said specific malignant disease is prostate carcinoma.  
     
     
         19 . The method according to  claim 14 , wherein the extent of binding of the monoclonal antibody to T-cells obtained from said tested individual is lower than the extent of binding of the same monoclonal antibody to T-cells of healthy individuals.  
     
     
         20 . The method according to  claim 19 , wherein said specific malignant disease is breast carcinoma or colon carcinoma.  
     
     
         21 . A composition comprising at least one monoclonal antibody of  claim 1  together with a carrier.  
     
     
         22 . A kit comprising at least one monoclonal antibody of  claim 1  together with a conjugate of a specific binding partner for said monoclonal antibody, and a label capable of producing a detectable signal.  
     
     
         23 . A method for the treatment of a malignant disease comprising administering to an individual in need a therapeutically effect amount of the composition of  claim 21 .  
     
     
         24 . The method according to  claim 23 , wherein said malignant disease is a solid tumor, prostate carcinoma, breast carcinoma, or colon carcinoma.  
     
     
         25 . A composition comprising of a therapeutically effective amount of one or more of the peptides of  claim 10 , together with a carrier.  
     
     
         26 . A method for the treatment of a malignant disease comprising administering to an individual in need a therapeutically effect amount of the composition of  claim 25 .  
     
     
         27 . The method according to  claim 26 , wherein said malignant disease is a solid tumor, prostate carcinoma, breast carcinoma, or colon carcinoma.