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 determining the suitability for treatment of a subject suffering from a disease, the method comprises:
 a. contacting a biological sample containing cells obtained from said subject with an antibody directed against a signal peptide (SP), or any fragment thereof, of a polypeptide associated with said disease; and   b. determining the expression level of said SP, or any fragment thereof, on the surface of cells in said biological sample,   wherein the presence of said SP, or any fragment thereof, on the surface of said cells in a level higher than a control level indicates that said subject is suitable for treatment.   
     
     
         2 . A method of diagnosing and treating a disease in a subject, the method comprises:
 a. contacting a biological sample containing cells obtained from said subject with an antibody directed against a signal peptide (SP), or any fragment thereof, of a polypeptide associated with said disease; and   b. determining the level of said SP, or any fragment thereof, on the surface of cells in said biological sample,   wherein the presence of a level of said SP in said sample which is higher than a control level is indicative of a disease in said subject;   c. treating a subject determined as having a disease.   
     
     
         3 . A method for detecting a disease in a subject, said method comprises:
 a. contacting a biological sample obtained from said subject with at least one SP, or any fragment thereof, of polypeptide associated with said disease; and   b. measuring the level of endogenous antibodies directed against said SP, or any fragment thereof, in said biological sample, wherein the presence of said endogenous antibodies in the sample in a level higher than a control is indicative of disease.   
     
     
         4 . The method according to  claim 1 , wherein said disease is cancer. 
     
     
         5 . The method according to  claim 1 , wherein said disease is a bacterial disease, a fungal disease, a parasite disease, a prion disease, or a viral disease. 
     
     
         6 . The method according to  claim 1 , wherein the polypeptide associated with said disease is a Tumor associated antigen (TAA). 
     
     
         7 . The method according to  claim 6 , wherein said TAA is selected from a group consisting of MUC1, Armet, HSP60, CANX, MTHFD2, FAP, MMP6, BAGE-1, GNTV, Q5H943, CEA, Pmel, Kallrkrein-4, Mammaglobin-1, MART-1, GPR143-OA1, PSA, TRP1, Tyrosinase, FGP-5, NEU proto-oncogene, Aft, MMP-2, PSMA, Telomerase-associated protein-2, PAP, Uroplakin II and Proteinase 3. 
     
     
         8 . The method according to  claim 7 , wherein said TAA is MUC1. 
     
     
         9 . The method according to to  claim 1 , wherein the polypeptide associated with said disease is MUC1 and wherein said SP, or any fragment thereof, is a peptide selected from a group consisting of the peptides denoted by SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10. 
     
     
         10 . The method according to  claim 4 , wherein said cancer is selected from a group consisting of multiple myeloma (MM), breast cancer, ovary cancer, colon cancer, rectal cancer, gastric cancer, non-small lung carcinoma (NScLC), renal cell carcinoma (RCC), transitional cell carcinoma (TCC), prostate cancer, pancreatic cancer, thyroid cancer, Squamous cell carcinoma (SCC), Thymic Carcinoma, lymphoma, leukemia, and Mesothelioma. 
     
     
         11 . The method according to  claim 10 , wherein said cancer is multiple myeloma (MM), breast cancer or ovarian cancer. 
     
     
         12 . The method according to  claim 5 , wherein said bacterial disease is caused by  Mycobacterium tuberculosis  (MTb). 
     
     
         13 . The method according to  claim 12 , wherein the polypeptide associated with said disease is selected from the group consisting of Antigen 85B, Lipoprotein IpqH, ATP dependent helicase putative, Uncharacterized protein Rv0476/MTO4941 precursor and Uncharacterized protein Rv1334/MT1376 precursor. 
     
     
         15 . The method according to  claim 1 , wherein said treatment comprises at least one of a vaccine capable of eliciting an immune response against said SP, or any fragment thereof and an agent capable of binding said SP, or any fragment thereof. 
     
     
         16 . The method according to  claim 15 , wherein said agent is at least one antibody, a ligand, or any fragment thereof which is capable of binding the SP expressed on said cells. 
     
     
         17 . The method according to  claim 1 , wherein said biological sample is selected from a group consisting of plasma, serum, whole blood, urine, sweat, lymph, faeces, cerebrospinal fluid, bone marrow biopsy or aspirate, or nipple aspiration.