Antibodies directed against signal peptides, methods and uses thereof

Abstract

The invention concerns methods employing antibodies directed against the signal peptide (SP) domain of various disease-associated polypeptides. These anti SP antibodies are capable of detecting cell surface expression of these SP domains and therefore they can be used in methods of diagnosis and/or therapy. In one aspect, the invention provides a method for determining the suitability for treatment of a subject suffering from a disease, whereby detection of cell surface expression of a specific SP indicates that the subject would benefit from therapy directed against this SP. The invention is specifically exemplified with antibodies directed against the signal peptide of MUC1 which is expressed on the surface of various cancer cells, and with signal peptide domains of Mycobacterium tuberculosis. In other aspects the invention provides methods for diagnosis of disease based on the detection of endogenously produced anti SP antibodies.

1 . A method for detecting cell surface expression of a MUC1 signal peptide (SP), the method comprising:
 a. obtaining a biological sample containing cells from a subject; and   b. determining the expression level of said MUC1 SP, by contacting a surface of cells in said biological sample with an antibody directed against a first 11 amino acids of said MUC1 SP, or any fragment thereof, and detecting the binding of said antibody and said first 11 amino acids of said MUC1 SP.   
     
     
         2 . The method of  claim 1 , wherein said antibodies are directed against a peptide selected from a group consisting of the peptides denoted by: SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. 
     
     
         3 . The method of  claim 2 , wherein said antibody is directed against a peptide denoted by SEQ ID NO: 3. 
     
     
         4 . A method for treatment of a subject suffering from a disease, the method comprising administering to said subject a therapeutically effective amount of at least one antibody directed against a first 11 amino acids of a MUC1 SP, or any fragment thereof. 
     
     
         5 . The method of  claim 4 , wherein said antibodies are directed against a peptide selected from a group consisting of the peptides denoted by: SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. 
     
     
         6 . The method of  claim 5 , wherein said antibody is directed against a peptide denoted by SEQ ID NO: 3. 
     
     
         7 . The method of  claim 4 , wherein said disease is cancer, a bacterial disease, a fungal disease, a parasitic disease, a prion disease, or a viral disease. 
     
     
         8 . The method of  claim 7 , wherein said disease is cancer. 
     
     
         9 . The method of  claim 8 , wherein said cancer is MUC1 positive cancer. 
     
     
         10 . The method of  claim 4 , wherein said antibody is an antibody that activates the complement system, or activates cellular cytotoxicity. 
     
     
         11 . The method of  claim 4 , wherein said antibody is associated with or combined with a cytotoxic moiety. 
     
     
         12 . The method of  claim 11 , wherein said cytotoxic moiety is selected from a radioactive agent, a toxin, an anti-metabolite, a chemotherapeutic agent, a drug, a growth inhibitory agent and an alkylating agent. 
     
     
         13 . The method of  claim 4 , wherein said antibody is associated with or combined with an imaging agent. 
     
     
         14 . The method of  claim 13 , wherein said imaging agent is a fluorophore. 
     
     
         15 . A kit, comprising:
 (a) at least one isolated antibody directed against a first 11 amino acids of a MUC1 signal peptide (SP), or any fragment thereof;   (b) means for detecting the binding of said isolated antibody to said MUC1 signal peptide; and   (c) optionally instructions for use of said kit.   
     
     
         16 . The kit of  claim 15 , wherein said antibody is directed against a peptide selected from a group consisting of the peptides denoted by: SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. 
     
     
         17 . The kit of  claim 16 , wherein said antibody is directed against a peptide denoted by SEQ ID NO: 3. 
     
     
         18 . The kit according to  claim 15 , wherein the kit further comprises a vaccine comprising the signal peptide, or a fragment thereof capable of eliciting an immune response, to said MUC1 SP. 
     
     
         19 . The kit of  claim 15 , for diagnosing cancer. 
     
     
         20 . The kit of  claim 19 , wherein said cancer is MUC1 positive cancer.