Anti-prostate cancer antibodies and methods of detection and treatment of prostate cancer using the same

Abstract

Disclosed herein are antibodies that detect a lipid-like antigen on prostate cancer cells and methods of detecting and treating prostate cancer using the same.

1 . A method of detecting the degree of differentiation of prostate cancer comprising contacting a sample of prostatic tissue with an anti-PCLA antibody, or functional fragment thereof, and correlating the amount of binding of said antibody to said sample with said degree of differentiation. 
     
     
         2 . The method of  claim 1  wherein the cancer is androgen independent. 
     
     
         3 . The method of  claim 1  wherein the cancer is metastatic. 
     
     
         4 . The method of  claim 1  wherein the sample is human. 
     
     
         5 . The method of  claim 1  wherein the degree of differentiation of prostate cancer is measured using a CDR, Fab, ScFv, or functional fragment of an anti-PCLA antibody. 
     
     
         6 . The method of  claim 1  wherein the antibody comprises at least one of a variable light chain nucleic acid sequence as set forth in SEQ ID NO:1 or a variable light chain nucleic acid sequence as set forth in SEQ ID NO:4. 
     
     
         7 . A method of determining the degree of differentiation of prostate cancer comprising contacting prostasomes with an anti-PCLA antibody or functional fragment thereof and correlating the amount of binding of said antibody to said prostasomes with said degree of differentiation. 
     
     
         8 . The method of  claim 7  wherein the prostasomes are present in semen or serum. 
     
     
         9 . A method of treating a subject having prostate cancer comprising assaying the degree of differentiation of said cancer and in response treating with an effective amount of an anti-PCLA antibody or functional fragment thereof. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . A method of preferentially inducing cell death in primary or metastatic prostate cancer cells over non-cancerous prostate cells in a human, comprising administering a humanized antibody CDR, Fab, ScFv, or functional fragment thereof derived from the antibody having a variable light chain sequence as set forth in SEQ ID NO:1 and a variable heavy chain sequence as set forth in SEQ ID NO:4. 
     
     
         16 . (canceled) 
     
     
         17 . A method of inhibiting prostate tumor growth in a patient having said tumor comprising administering a humanized antibody CDR, Fab, ScFv, or functional fragment thereof derived from the antibody having a variable light chain sequence as set forth in SEQ ID NO:1 and a variable heavy chain sequence as set forth in SEQ ID NO:4. 
     
     
         18 . An antibody derived from the antibody having a variable light chain sequence as set forth in SEQ ID NO:1 or a variable heavy chain sequence as set forth in SEQ ID NO:4. 
     
     
         19 . The antibody of  claim 18  further bound to PCLA. 
     
     
         20 . The antibody bound to PCLA as set forth in  claim 19 , wherein the PCLA is on human prostasomes. 
     
     
         21 . The antibody bound to PCLA as set forth in  claim 19 , wherein the PCLA is present on metastatic or androgen independent human prostatic cancer tissue. 
     
     
         22 . An antibody or antibody functional fragment that binds to B-III dodecaosylceramide or B-IV tetradecaosylceramide; provided that the antibody is not F77 MAb. 
     
     
         23 . The antibody or antibody functional fragment of  claim 22  wherein said antibody or antibody functional fragment competes for binding with F77 MAb. 
     
     
         24 . The antibody or antibody functional fragment of  claim 23  wherein said antibody or antibody functional fragment competes for binding with F77 MAb to B-III dodecaosylceramide or B-IV tetradecaosylceramide. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The antibody or antibody functional fragment of  claim 22 , wherein said antibody or antibody functional fragment is humanized. 
     
     
         28 . The antibody or antibody functional fragment of  claim 22  wherein said antibody or antibody functional fragment is conjugated to a toxin or cytotoxic agent. 
     
     
         29 . A method of detecting the degree of differentiation of prostate cancer comprising contacting a sample of prostatic tissue with the antibody or antibody functional fragment of  claim 22 , and correlating the amount of binding of said antibody to said sample with said degree of differentiation. 
     
     
         30 . A method of determining the degree of differentiation of prostate cancer comprising contacting prostasomes with the antibody or antibody functional fragment of  claim 22  and correlating the amount of binding of said antibody to said prostasomes with said degree of differentiation. 
     
     
         31 . A method of treating a subject having prostate cancer comprising assaying the degree of differentiation of said cancer and in response treating with an effective amount of the antibody or antibody functional fragment of  claim 22 . 
     
     
         32 . A method of preferentially inducing cell death in primary or metastatic prostate cancer cells over non-cancerous prostate cells in a human, comprising administering the antibody or antibody functional fragment of  claim 22 . 
     
     
         33 . A method of inhibiting prostate tumor growth in a patient having said tumor comprising administering the antibody or antibody functional fragment of  claim 22 .