Peptides and antibodies to muc 1 proteins

Abstract

The invention relates to methods of inhibiting proliferation or growth of tumor cells and/or inducing cell death relates to the use of antibodies, hybridomas and pharmaceutical compositions containing same, for inhibiting growth or proliferation and inducing death in epithelial, colon, lung, breast and ovarian tumor cells or other cells which express MUC1 proteins.

1 . A method of inhibiting mammalian cell proliferation or cell growth comprising the step of administering to a subject in need, an effective amount of a ligand which specifically binds to an epitope in the extracellular region of a transmembrane isoform of MUC1 protein, thereby selectively inhibiting mammalian cell proliferation or cell growth.  
     
     
         2 . A method of inducing mammalian cell death comprising the step of administering to a subject in need, an effective amount of a ligand which specifically binds to an epitope in the extracellular region of a transmembrane isoform of MUC1 protein, thereby selectively inducing mammalian cell death.  
     
     
         3 . A method of treating a subject with a disease involving pathological proliferation of cells comprising the step of administering to a subject in need, an effective amount of a ligand which specifically binds to an epitope in the extracellular region of a transmembrane isoform of MUC1 protein, thereby treating the disease.  
     
     
         4 . A method of selectively inhibiting cell proliferation or cell growth comprising the steps of contacting a cell which expresses MUC1 protein isoform with an effective amount of a ligand which specifically binds to an epitope in the extracellular region of the transmembrane isoform of the MUC1 protein, thereby selectively inhibiting the cell proliferation or cell growth.  
     
     
         5 . A method of selectively inducing cell death comprising the step of contacting a cell which expresses MUC1 protein isoform with an effective amount of a ligand which specifically binds to an epitope in the extracellular region of the transmembrane isoform of MUC1 protein, thereby selectively inducing cell death.  
     
     
         6 . The method according to  claims 1  to  5 , wherein said cell is a cancer cell.  
     
     
         7 . The method according to  claim 6 , wherein said cancer cell is an epithelial cancer cell.  
     
     
         8 . The method according to  claim 7 , wherein said epithelial cancer cell is a breast cancer cell, an ovarian cancer cell, a lung cancer cell or a colon cancer cell.  
     
     
         9 . The method according to  claims 1  to  5 , wherein said MUC1 isoform is MUC1/Y, MUC1/REP, or MUC1/X.  
     
     
         10 . The method according to  claims 1  to  5 , wherein said ligand is an antibody, a peptide, an antagonist, or an agonist.  
     
     
         11 . The method according to  claims 1  to  5 , wherein said epitope is an amino acid sequence within a 59 amino acid sequence as set forth in SEQ ID No.1.  
     
     
         12 . The method according to  claims 1  to  5 , wherein said ligand is conjugated to a cytotoxic drug.  
     
     
         13 . The method according to  claim 10 , wherein said antibody is a monoclonal antibody, a synthetic antibody, a polyclonal antibody or a chimera.  
     
     
         14 . A method of treating a subject with a disease involving pathological proliferation of cells comprising the step of administering to a subject in need, an effective amount of a peptide which comprises an amino acid sequence corresponding to the extracellular region of a transmembrane isoform of MUC1 protein, so as to induce an increase in the level of antibodies specific for said peptide in the subject, thereby treating the disease.  
     
     
         15 . The method according to  claim 14  wherein said MUC1 isoform is MUC1/Y, MUC1/REP, or MUC1/X.  
     
     
         16 . The method according to  claim 14  wherein said peptide comprises an amino acid sequence within a 59 amino acid sequence as set forth in SEQ ID No.1.  
     
     
         17 . An isolated antibody which specifically binds to an epitope in the extracellular region of a transmembrane isoform of MUC1 protein.  
     
     
         18 . The isolated antibody according to  claim 17 , wherein said isoform of MUC1 protein is MUC1/Y protein, MUC1/REP protein or MUC1/X protein.  
     
     
         19 . The isolated antibody according to  claim 17 , wherein the antibody is a monoclonal antibody, a synthetic antibody, a polyclonal antibody or a chimera.  
     
     
         20 . The antibody according to  claim 17  wherein said epitope is an amino acid sequence within a 59 amino acid sequence as set forth in SEQ ID No.1.  
     
     
         21 . A hybridoma cell producing a monoclonal antibody that binds to an epitope in the extracellular region of a transmembrane isoform of MUC1 protein.  
     
     
         22 . The hybriodoma of  claim 21 , wherein said isoform of MUC1 protein is MUC1/Y protein, MUC1/REP protein or MUC1/X protein.  
     
     
         23 . A pharmaceutical composition comprising an effective amount of a ligand which specifically binds to an epitope within a transmembrane isoform of MUC1 protein and a pharmaceutically acceptable carrier.  
     
     
         24 . The pharmaceutical composition of  claim 23  wherein said ligand is conjugated to a cell killing agent.  
     
     
         25 . The pharmaceutical composition of  claim 23 , wherein said MUC1 isoform is MUC1/Y, MUC1/REP or MUC1/X.  
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein said epitope is an amino acid sequence within a 59 amino acid sequence as set forth in SEQ ID No.1  
     
     
         27 . The pharmaceutical composition of  claim 23 , wherein said ligand is an antibody, a peptide, an antagonist or an agonist.  
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein the antibody is a monoclonal antibody, a synthetic antibody, a polyclonal antibody or a chimera.