Radioactive metal-labeled anti-cadherin antibody
An object of the present invention is to provide a radioactive metal anti-cadherin antibody which is highly accumulated specifically in cancer tissue. Another object is to provide a cancer therapeutic agent having high anti-cancer effect and safety and a cancer diagnostic agent. The radioactive metal-labeled anti-cadherin antibody is obtained by binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent.
1. A radioactive metal-labeled anti-p-cadherin antibody, obtained by a process comprising binding a radioactive metallic element to an anti-p-cadherin antibody via a metal-chelating reagent,
wherein the anti-p-cadherin antibody is a monoclonal antibody produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899 or NITE BP-1040, or a recombinant antibody thereof or a chimeric antibody thereof or a humanized antibody thereof.
2. The radioactive metal-labeled anti-p-cadherin antibody of claim 1 , wherein the anti-p-cadherin antibody is a monoclonal antibody, produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899, NITE BP-1040, NITE BP-1044, NITE BP-1048, NITE BP-1049, or NITE BP-1050, or a recombinant antibody thereof.
3. The radioactive metal-labeled anti-p-cadherin antibody of claim 1 , wherein the metal-chelating reagent is selected from the group consisting of isothiocyanobenzyl DOTA, methylisothiocyanobenzyl DTPA, and cyclohexylisothiocyanobenzyl DTPA.
4. The radioactive metal-labeled anti-p-cadherin antibody of claim 1 , wherein a mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.1 to 1:4.5.
5. The radioactive metal-labeled anti-p-cadherin antibody of claim 4 , wherein the mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.5 to 1:3.
6. The radioactive metal-labeled anti-p-cadherin antibody of claim 1 , wherein the radioactive metallic element is a cytotoxic radioactive metal suitable for treating a p-cadherin expressing cancer.
7. The radioactive metal-labeled anti-p-cadherin antibody of claim 6 , wherein the cytotoxic radioactive metal is selected from the group consisting of yttrium-90 ( 90 Y), rhenium-186 ( 186 Re), rhenium-188 ( 188 Re), copper-67 ( 67 Cu), iron-59 ( 59 Fe), strontium-89 ( 89 Sr), gold-198 ( 198 Au), dysprosium-165 ( 165 Dy), ruthenium-103 ( 103 Ru), holmium-166 ( 166 Ho), samarium-153 ( 153 Sm), and lutetium-177 ( 177 Lu).
8. The radioactive metal-labeled anti-p-cadherin antibody of claim 6 , wherein the cytotoxic radioactive metal is yttrium-90 ( 90 Y).
9. The radioactive metal-labeled anti-p-cadherin antibody of claim 6 , wherein the cancer therapy is suitable for treating a p-cadherin-expressing cancer.
10. The radioactive metal-labeled anti-p-cadherin antibody of claim 1 , wherein the radioactive metallic element is a non-cytotoxic radioactive metal suitable for diagnosing p-cadherin expressing cancer.
11. The radioactive metal-labeled anti-p-cadherin antibody of claim 10 , wherein the non-cytotoxic radioactive metal is selected from the group consisting of technetium-99m ( 99m Tc), indium-111 ( 111 In), indium-113m ( 113m In), gallium-67 ( 67 Ga), gallium-68 ( 68 Ga), thallium-201 ( 201 T 1 ), cobalt-57 ( 57 Co), strontium-85 ( 85 Sr), and copper-64 ( 64 Cu).
12. The radioactive metal-labeled anti-p-cadherin antibody of claim 10 , wherein the non-cytotoxic radioactive metal is indium- 111 ( 111 In) or copper-64 ( 64 Cu).
13. A p-cadherin expressing cancer therapeutic agent comprising, as an active ingredient, the radioactive metal-labeled anti-p-cadherin antibody of claim 6 .
14. A p-cadherin expressing cancer diagnostic agent comprising, as an active ingredient, the radioactive metal-labeled anti-p-cadherin antibody of claim 10 .
15. An antibody-producing cell deposited as an accession number of NITE BP-897, NITE BP-898, NITE BP-899, NITE BP-1040, NITE BP-1044, NITE BP-1048, NITE BP-1049, or NITE BP-1050.
16. A metal chelating reagent-binding anti-p-cadherin antibody, obtained by a process comprising binding a metal-chelating reagent to an anti-p-cadherin antibody, wherein the anti-p-cadherin antibody is a monoclonal antibody produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899, or NITE BP-1040, or a recombinant antibody thereof or a chimeric antibody thereof or a humanized antibody thereof.
17. The metal-chelating reagent-binding anti-p-cadherin antibody of claim 16 , wherein the anti-p-cadherin antibody is a monoclonal antibody produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899, NITE BP-1040, NITE BP-1044, NITE BP-1048, NITE BP-1049, or NITE BP-1050, or a recombinant antibody thereof.
18. The metal-chelating reagent-binding anti-p-cadherin antibody of claim 16 , wherein the metal-chelating reagent is selected from the group consisting of isothiocyanobenzyl DOTA, methylisothiocyanobenzyl DTPA, and cyclohexylisothiocyanobenzyl DTPA.
19. The metal-chelating reagent-binding anti-p-cadherin antibody of claim 16 , wherein a mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.1 to 1:4.5.
20. The metal-chelating reagent-binding anti-p-cadherin antibody of claim 19 , wherein the mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.5 to 1:3.
21. An anti-p-cadherin antibody which is a monoclonal antibody produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899, or NITE BP-1040, or a recombinant antibody thereof or a chimeric antibody thereof or a humanized antibody thereof.
22. An anti-p-cadherin antibody which is a monoclonal antibody produced by an antibody-producing cell of an accession number of NITE BP-897, NITE BP-898, NITE BP-899, NITE BP-1040, NITE BP-1044, NITE BP-1048, NITE BP-1049, or NITE BP-1050 or a recombinant antibody thereof.
23. A method for treating a p-cadherin expressing cancer, comprising:
administering an effective amount of the radioactive metal-labeled anti-cadherin antibody of claim 6 to a subject in need thereof.
24. A cancer diagnosis method of diagnosing a p-cadherin expressing cancer, comprising:
administering an effective amount of the radioactive metal-labeled anti-cadherin antibody of claim 10 to a subject in need thereof; and
diagnosing the p-cadherin expressing cancer.