csPCNA Isoform Antibodies And Uses Thereof

Abstract

Antibodies specifically bind only to a cancer specific proliferating cell nuclear antigen (csPCNA) isoform and not to the non-malignant proliferating cell nuclear antigen (nmPCNA) isoform. Methods and compositions to detect the presence of csPCNA isoform are disclosed.

We claim: 
     
         1 . A method for reducing tumor progression in a subject, comprising:
 administering a pharmaceutically acceptable composition comprising a formulation of a therapeutically effective amount of cancer specific proliferating cell nuclear antigen (csPCNA) isoform-specific antibody that specifically binds cancer specific proliferating cell nuclear antigen (csPCNA) isoform, wherein the antibody does not bind to non-malignant proliferating cell nuclear antigen (nmPCNA), and wherein the antibody binds to an epitope of csPCNA comprising an amino acid sequence selected from LGIPEQEY (SEQ ID NO: 1), QLGIPEQEY (SEQ ID NO: 9), LGIPEQEYSCVV (SEQ ID NO: 13), LGIPEQEYSCV (SEQ ID NO: 14), and LGIPEQEYSC (SEQ ID NO: 15); and a delivery component to an individual having a tumor.   
     
     
         2 . The method of  claim 1 , wherein the formulation comprises a liposome or a nanoparticle. 
     
     
         3 . The method of  claim 1 , wherein the formulation comprises a tumor killing agent or an immune enhancing agent. 
     
     
         4 . A method of determining the presence of malignant cells, the method comprising:
 contacting a biological sample suspected of containing auto-antibodies, to a substrate comprising bound cancer specific proliferating cell nuclear antigen (csPCNA) isoform or fragments thereof, wherein the autoantibodies bind to a csPCNA isoform but do not bind to non-malignant proliferating cell nuclear antigen (nmPCNA);   providing conditions for csPCNA-auto-antibody complex formation; and   detecting the presence of the auto-antibody-csPCNA complex in the biological sample.   
     
     
         5 . The method of  claim 4 , wherein the presence of the autoantibody-csPCNA complex is detected using an anti-human secondary antibody. 
     
     
         6 . The method of  claim 4 , wherein the presence of the autoantibody-csPCNA complex is detected using a labeled biological sample. 
     
     
         7 . The method of  claim 4 , wherein the biological sample is selected from the group consisting of blood, plasma, lymph, serum, pleural fluid, spinal fluid, saliva, sputum, urine, gastric juice, pancreatic juice, ascites fluid, synovial fluid, milk, and semen. 
     
     
         8 . A method of detecting the presence of a circulating cancer specific proliferating cell nuclear antigen (csPCNA) isoform, the method comprising detecting an auto-antibody that binds to a csPCNA isoform but do not bind to non-malignant proliferating cell nuclear antigen (nmPCNA) in a biological sample and thereby determining the presence of circulating csPCNA isoform. 
     
     
         9 . The method of  claim 8 , wherein the csPCNA isoform is detected by determining the presence of auto-antibodies to csPCNA isoform. 
     
     
         10 . The method of  claim 8 , wherein the csPCNA isoform is detected by an antibody specific to the csPCNA isoform.