Cell surface prostate cancer antigen for diagnosis

Abstract

The present invention provides compositions and methods of detecting prostate cancer in the body fluids or tissues of patients. Prostate cancer is detected by measuring the level of glypican-1 in a body fluid sample. In one embodiment prostate cancer is detected by contacting a body fluid sample with an anti-glypican-1 antibody, such as MIL-38. The invention includes kits for detection of prostate cancer in a body fluid sample, comprising an anti-glypican-1 antibody and glypican-1 standards.

1 - 29 . (canceled) 
     
     
         30 . A method of detecting prostate cancer in a patient, the method comprising measuring the level of soluble glypican-1 in a body fluid sample from a patient and determining that said patient has prostate cancer based upon the level of soluble glypican-1 in the body fluid sample, wherein:
 the measuring of soluble glypican-1 in the body fluid sample comprises contacting the body fluid sample with anti-glypican-1 antibodies.   
     
     
         31 . The method of detecting prostate cancer in a patient of  claim 30 , comprising the steps of:
 (a) obtaining a body fluid sample from a patient;   (b) contacting said body fluid sample with the anti-glypican-1 antibodies of claim  1 ; and   (c) determining that said patient has prostate cancer based upon binding of the anti-glypican-1 antibodies to said body fluid sample.   
     
     
         32 . The method of  claim 30 , wherein the anti-glypican-1 antibodies do not comprise a light chain variable region comprising:
 a complementarity determining region 1 (CDR1) comprising the amino acid sequence positions 48-58 of SEQ ID NO: 12;   a complementarity determining region 2 (CDR2) comprising the amino acid sequence positions 74-80 of SEQ ID NO: 12; and/or   a complementarity determining region 3 (CDR3) comprising the amino acid sequence positions 113-121 of SEQ ID NO: 12.   
     
     
         33 . The method of  claim 31 , wherein the anti-glypican-1 antibodies comprise antibody fragments or recombinant antibodies capable of binding specifically to glypican-1. 
     
     
         34 . The method of  claim 30 , wherein the anti-glypican-1 antibodies are labeled. 
     
     
         35 . The method of  claim 34 , wherein said label is chosen from a group consisting of a radiolabel, a fluorescent label, a biotin-avidin amplification system, a chemiluminescence system, microspheres, and colloidal gold. 
     
     
         36 . The method of  claim 30 , wherein binding of the anti-glypican-1 antibodies to soluble glypican-1 in the body fluid sample is detected via a technique selected from the group consisting of immunofluorescence, radiolabeling, immunoblotting, Western blotting, enzyme linked immunosorbent assay (ELISA), flow cytometry, immunoprecipitation, immunohistochemistry, biofilm test, affinity ring test, antibody array optical density test, and chemiluminescence. 
     
     
         37 . The method of  claim 30 , wherein said level of glypican-1 in the body fluid sample from a patient is compared to the level of glypican-1 in a control sample; wherein increased anti-glypican-1 antibody binding of the body fluid sample over the control sample is associated with the presence of prostate cancer. 
     
     
         38 . The method of  claim 37 , wherein a 50% or more increase in the level of glypican-1 of said body fluid sample over the level of glypican-1 in the control sample is indicative of prostate cancer. 
     
     
         39 . The method of  claim 30 , wherein binding of the anti-glypican-1 antibodies to said body fluid sample is compared to binding of anti-glypican-1 antibodies in a control sample; wherein increased anti-glypican-1 antibody binding of the body fluid sample over the control sample is associated with the presence of prostate cancer. 
     
     
         40 . The method of  claim 39 , wherein a 50% or more increase in the anti-glypican-1 antibody binding to said body fluid sample over the level of anti-glypican-1 antibody binding of the control sample is indicative of prostate cancer. 
     
     
         41 . The method of  claim 30 , wherein binding of the anti-glypican-1 antibodies to said body fluid sample is compared to binding of the anti-glypican-1 antibodies to one or more glypican-1 standards; wherein the anti-glypican-1 antibody binding of the standards is used to quantify the amount of glypican-1 in said body fluid sample. 
     
     
         42 . The method of  claim 30 , wherein a glypican-1 content higher than about 10 ng/ml in the body fluid sample is indicative of prostate cancer. 
     
     
         43 . The method of  claim 30 , further comprising:
 measuring the level of prostate-specific antigen (PSA) in a body fluid sample from the patient, and   determining that said patient has prostate cancer based upon (i) the level of PSA measured in the body fluid sample, and (ii) binding of said anti-glypican-1 antibodies to said body fluid sample.   
     
     
         44 . The method of  claim 43 , wherein the level of prostate-specific antigen (PSA) is measured in a blood sample from the patient. 
     
     
         45 . The method of  claim 43 , wherein the level of prostate-specific antigen (PSA) in the body fluid sample measured is compared to the level of PSA measured in a control sample; wherein increased PSA levels in the body fluid sample over the control sample is associated with the presence of prostate cancer. 
     
     
         46 . The method of  claim 30 , wherein said body fluid is selected from the group consisting of blood, serum, plasma, and urine. 
     
     
         47 . The method of  claim 30 , wherein the anti-glypican-1 antibodies do not comprise:
 (a) a heavy chain variable region comprising:
 a complementarity determining region 1 (CDR1) comprising or consisting of an amino acid sequence defined by positions 50-54 of SEQ ID NO: 10; 
 a complementarity determining region 2 (CDR2) comprising or consisting of an amino acid sequence defined by positions 69-85 of SEQ ID NO:10; 
 a complementarity determining region 3 (CDR3) comprising or consisting of an amino acid sequence defined by positions 118-126 of SEQ ID NO: 10; and 
   (b) a light chain variable region comprising:
 a complementarity determining region 1 (CDR1) comprising or consisting of an amino acid sequence defined by positions 44-54 of SEQ ID NO: 11; 
 a complementarity determining region 2 (CDR2) comprising or consisting of an amino acid sequence defined by positions 70-76 of SEQ ID NO: 11; 
 a complementarity determining region 3 (CDR3) comprising or consisting of an amino acid sequence defined by positions 109-117 of SEQ ID NO: 11; and 
   antibodies of the population do not comprise a light chain variable region comprising: a complementarity determining region 1 (CDR1) comprising or consisting of an amino acid sequence defined by positions 48-58 of SEQ ID NO: 12;
 a complementarity determining region 2 (CDR2) comprising or consisting of an amino acid sequence defined by positions 74-80 of SEQ ID NO: 12; 
 a complementarity determining region 3 (CDR3) comprising or consisting of an amino acid sequence defined by positions 113-121 of SEQ ID NO: 12. 
   
     
     
         48 . The method of  claim 30 , wherein the anti-glypican-1 antibodies do not comprise MIL-38 antibody. 
     
     
         49 . The method of  claim 30 , wherein the anti-glypican-1 antibodies comprise polyclonal anti-glypican-1 antibodies.