Methods of treating prostate cancer with anti-prostate specific membrane antigen antibodies

Abstract

Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.

We claim: 
     
         1 . A method of targeting a non-prostate cancer associated with vascular endothelial cells expressing prostate specific membrane antigen (PSMA) in a subject, the method comprising administering to the subject a first dose of an anti-PSMA antibody, or antigen binding fragment thereof, the first dose comprising an amount of an anti-PSMA antibody, or antigen binding fragment thereof, effective to target the non-prostate cancer associated with vascular endothelial cells expressing PSMA, wherein the anti-PSMA antibody comprises: a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:22, the amino acid sequence encoded by the nucleotide sequence shown as nucleotide residues 261-581 of SEQ ID NO:25, or the light chain variable region amino acid sequence of the antibody produced by the NS0 cell line having ATCC Accession Number PTA-3709; and a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:21, the amino acid sequence encoded by the nucleotide sequence shown as nucleotide residues 261-605 of SEQ ID NO:23, or the heavy chain variable region amino acid sequence of the antibody produced by the cell line having ATCC Accession Number PTA-3709. 
     
     
         2 . The method of  claim 1 , wherein the amount of an anti-PSMA antibody, or antigen binding fragment thereof, effective to target the non-prostate cancer associated with vascular endothelial cells expressing PSMA is selected from the group consisting of 5 mg, 10 mg, 20 mg, 40 mg, or 80 mg. 
     
     
         3 . The method of  claim 1 , further comprising administering a second dose of the anti-PSMA antibody, or antigen binding fragment thereof, 14 days after the first dose of the anti-PSMA antibody, or antigen binding fragment thereof. 
     
     
         4 . The method of  claim 1 , wherein the anti-PSMA antibody comprises two heavy chains and two light chains. 
     
     
         5 . The method of  claim 1 , wherein the anti-PSMA antibody, or antigen binding fragment thereof, is conjugated to a molecular entity. 
     
     
         6 . The method of  claim 5 , wherein the molecular entity is a therapeutic agent. 
     
     
         7 . The method of  claim 6 , wherein the therapeutic agent is a radioactive isotope. 
     
     
         8 . The method of  claim 7 , wherein the radioactive isotope is  111 In. 
     
     
         9 . The method of  claim 5 , wherein the molecular entity is a label. 
     
     
         10 . The method of  claim 1 , further comprising administering one or more cytotoxic agents. 
     
     
         11 . The method of  claim 1 , further comprising administering one or more immunomodulatory agents. 
     
     
         12 . The method of  claim 1 , wherein the subject is a human.