Forms of Prostate Specific Antigens and Methods for their Detection

Abstract

Inactive precursor forms of PSA (pPSA) have been identified to exist in serum and tissues of patients with prostate cancer. Antibodies specific for pPSA are provided. Methods for detecting inactive precursors of PSA in human physiological fluid and tissues are also provided, as well as diagnostic kits and methods useful in the diagnosis and management of prostate cancer.

1 - 20 . (canceled) 
     
     
         21 . A method of detecting the presence of prostate cancer in a subject comprising the steps of:
 (a) contacting a PSA containing sample from the subject with an antibody or antigen binding fragment thereof selective for proPSA, wherein the PSA containing sample is selected from the group consisting of prostate tissue, prostate cells from prostate tissue, blood, serum, plasma, seminal fluid, and urine;   (b) determining the amount of proPSA contained in the PSA containing sample;   (c) correlating the amount of the proPSA contained in the PSA containing sample to the presence of prostate cancer in the subject,   wherein step (c) further comprises the steps of:   (i) contacting the PSA containing sample with an antibody or antigen binding fragment thereof selective for total PSA;   (ii) determining the amount of total PSA contained in the PSA containing sample; and   (iii) comparing the amount of proPSA to the amount of total PSA to generate a ratio for determining the presence of prostate cancer,   wherein a value of the ratio greater than a cut-off value is an indication of prostate cancer in the subject.   
     
     
         22 - 43 . (canceled) 
     
     
         44 . The method of  claim 21 , wherein the proPSA is selected from the group consisting of [−2], [−4], [−5] and [−7]proPSA. 
     
     
         45 . The method of  claim 21  wherein step (a) comprises:
 (i) contacting the PSA containing sample with the antibody or antigen binding fragment thereof under conditions that allow the formation of a binary complex comprising the antibody or antigen binding fragment thereof and the proPSA if present in the sample; and   (ii) determining the amount of the complex.   
     
     
         46 . The method of  claim 21 , wherein the antibody selective for proPSA is a monoclonal antibody. 
     
     
         47 . The method of  claim 21 , wherein the antibody selective for proPSA is attached to a solid support. 
     
     
         48 . The method of  claim 47 , wherein the solid support is selected from a microtiter plate and a bead. 
     
     
         49 . The method of  claim 45 , wherein the complex is detected by a second antibody or antigen binding fragment thereof which comprises a detectable label or which is capable of binding to a detectable label for forming a detectable complex. 
     
     
         50 . The method of  claim 21 , wherein the antibody selective for total PSA is a monoclonal antibody. 
     
     
         51 . The method of  claim 21 , wherein the antibody selective for total PSA is attached to a solid support. 
     
     
         52 . The method of  claim 51 , wherein the solid support is selected from a microtiter plate and a bead. 
     
     
         53 . A method for detecting the presence of prostate cancer in a subject comprising the steps of:
 (a) contacting a PSA containing sample from the subject with an antibody or antigen binding fragment thereof selective for proPSA, wherein the PSA containing sample is selected from the group consisting of prostate tissue, prostate cells from prostate tissue, blood, serum, plasma, seminal fluid, and urine;   (b) determining the amount of proPSA contained in the PSA containing sample;   (c) correlating the amount of the proPSA contained in the PSA containing sample to the presence of prostate cancer in the subject,   wherein step (c) further comprises the steps of:
 (i) contacting the PSA containing sample with an antibody or antigen binding fragment thereof selective for total PSA; 
 (ii) determining the amount of total PSA contained in the PSA containing sample; and 
 (iii) comparing the amount of total PSA to the amount of proPSA to generate a ratio for determining the presence of prostate cancer, 
   wherein a value of the ratio less than a cut-off value is an indication of prostate cancer in the subject.   
     
     
         54 . The method of  claim 53 , wherein the proPSA is selected from the group consisting of [−2], [−4], [−5] and [−7]proPSA. 
     
     
         55 . The method of  claim 53  wherein step (a) comprises:
 (i) contacting the PSA containing sample with the antibody or antigen binding fragment thereof under conditions that allow the formation of a binary complex comprising the antibody or antigen binding fragment thereof and the proPSA if present in the sample; and,   (ii) determining the amount of the complex.   
     
     
         56 . The method of  claim 53 , wherein the antibody selective for proPSA is a monoclonal antibody. 
     
     
         57 . The method of  claim 53 , wherein the antibody selective for proPSA is attached to a solid support. 
     
     
         58 . The method of  claim 57 , wherein the solid support is selected from a microtiter plate and a bead. 
     
     
         59 . The method of  claim 55 , wherein the complex is detected by a second antibody or antigen binding fragment thereof which comprises a detectable label or which is capable of binding to a detectable label for forming a detectable complex. 
     
     
         60 . The method of  claim 53 , wherein the antibody selective for total PSA is a monoclonal antibody. 
     
     
         61 . The method of  claim 53 , wherein the antibody selective for total PSA is attached to a solid support. 
     
     
         62 . The method of  claim 61 , wherein the solid support is selected from a microtiter plate and a bead.