Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
View Patent ↗The present invention relates to monoclonal antibodies that bind to the extracellular domain of prostate-specific membrane antigen (PSMA), hybridoma cell lines producing the antibodies, and methods of using such antibodies for diagnosis and treatment of cancer. In particular, thirty-five monoclonal antibodies reactive with PSMA expressed on the cell surface are exemplified. Additionally, the present invention relates to a novel protein variant (PSM′) of the PSMA detected by a number of the antibodies of the invention. The hydrolase activity of PSMA and PSM′ allows the use of an immunoenzymatic assay for their detection.
1. A monoclonal antibody having an antigen-binding region which binds to a native conformation of prostate specific membrane antigen (PSMA) on the surface of live cells and not to denatured PSMA.
2. The antibody of claim 1 in which PSMA comprises an extracellular domain comprising the amino acid sequence from residue #44 to 750 as depicted in FIG. 1 (SEQ ID NO:2).
3. A kit for diagnosis, prognosis, or monitoring prostate cancer, comprising the monoclonal antibody according to claim 1 or an antigen-binding fragment thereof.
4. A kit for diagnosis, prognosis or monitoring prostate cancer, comprising the monoclonal antibody according to claim 2 or an antigen-binding fragment thereof.
5. The antibody of claim 1 , wherein the antibody is produced by a hybridoma selected from the group consisting of 3C6 having ATCC accession number HB 12491, 4D4 having ATCC accession number HB 12493, and 1G9 having ATCC accession number HB 12495.
6. A monoclonal antibody having an antigen-binding region which binds to a native conformation of PSMA on the surface of live cells and not to denatured PSMA and not to PSMA on the surface of fixed cells.
7. A kit for diagnosis, prognosis, or monitoring prostate cancer, comprising the monoclonal antibody according to claim 6 , or an antigen-binding fragment thereof.
8. A composition comprising the monoclonal antibody of claim 6 .
9. The monoclonal antibody of claim 6 , wherein the antibody does not bind to denatured PSMA.
10. The monoclonal antibody of claim 6 , wherein the antibody does not bind to PSMA on the surface of fixed cells.
11. The monoclonal antibody of claim 6 , wherein the monoclonal antibody is produced by a hybridoma selected from the group consisting of 3C6 having ATCC accession number HB 12491, 4D4 having ATCC accession number HB 12493, and 1G9 having ATCC accession number HB 12495.
12. A monoclonal antibody having an antigen-binding region which binds to a native conformation of PSMA on the surface of live cells and not to PSMA on the surface of fixed cells.
13. The monoclonal antibody of claim 12 , wherein the monoclonal antibody is produced by a hybridoma selected from the group consisting of 3C6 having ATCC accession number HB 12491, 4D4 having ATCC accession number HB 12493, and 1G9 having ATCC accession number HB 12495.
14. A composition comprising the monoclonal antibody of claim 12 .
15. A kit comprising the monoclonal antibody of claim 10 or an antigen-binding fragment thereof.
16. A kit comprising the monoclonal antibody of claim 11 or an antigen-binding fragment thereof.
17. A kit comprising the monoclonal antibody of claim 12 or an antigen-binding fragment thereof.
18. A composition comprising the monoclonal antibody of claim 1 .
19. A kit for diagnosis, prognosis or monitoring prostate cancer, comprising the monoclonal antibody according to claim 9 or an antigen-binding fragment thereof.
20. The kit according to claim 3 , 4 , 7 , 19 , 15 , 16 , or 17 , in which the antibody or fragment thereof is packaged in an aqueous medium or in lyophilized form.