Radioactive metal-labeled anti-cadherin antibody

Abstract

A radioactive metal-labeled anti-cadherin antibody which is obtained by binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent.

1 : A radioactive metal-labeled anti-cadherin antibody, which is obtained by binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent,
 wherein a mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.1 to 1:4.5.   
     
     
         2 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 1 , wherein the mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.5 to 1:3. 
     
     
         3 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 1 , wherein the anti-p-cadherin antibody is bonded to a region 1 to 655 of SEQ ID NO:2. 
     
     
         4 : 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. 
     
     
         5 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 1 , wherein the anti-p-cadherin antibody is a monoclonal antibody, a recombinant antibody, a chimeric antibody thereof, a humanized antibody, or a fragment thereof. 
     
     
         6 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 1 , wherein the radioactive metallic element is 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 1 , wherein the radioactive metallic element is non-cytotoxic radioactive metal suitable for diagnosing a p-cadherin expressing cancer. 
     
     
         10 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 9 , 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 Tl), cobalt-57 ( 57 Co), strontium-85 ( 85 Sr), and copper-64 ( 64 Cu). 
     
     
         11 : The radioactive metal-labeled anti-p-cadherin antibody of  claim 9 , the non-cytotoxic radioactive metal is indium-111 ( 111 In) or copper-64 ( 64 Cu). 
     
     
         12 : A p-cadherin expressing cancer therapeutic agent comprising as an active ingredient the radioactive metal-labeled anti-p-cadherin antibody of  claim 6 . 
     
     
         13 : A p-cadherin expressing cancer diagnosing agent comprising as an active ingredient the radioactive metal-labeled anti-p-cadherin antibody of  claim 9 . 
     
     
         14 : 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 a mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.1 to 1:4.5.   
     
     
         15 : The metal chelating reagent-binding anti-p-cadherin antibody of  claim 14 , wherein the mole ratio of the anti-p-cadherin antibody to the metal-chelating reagent is from 1:0.5 to 1:3. 
     
     
         16 : The metal chelating reagent-binding anti-p-cadherin antibody of  claim 14 , wherein the anti-p-cadherin antibody is bonded to a region 1 to 655 of SEQ ID NO:2 
     
     
         17 : The metal chelating reagent-binding anti-p-cadherin antibody of  claim 14 , wherein the metal-chelating reagent is selected from the group consisting of isothiocyanobenzyl DOTA, methylisothiocyanobenzyl DTPA and cyclohexylisothiocyanobenzyl DTPA. 
     
     
         18 : The metal chelating reagent-binding anti-p-cadherin antibody of  claim 14 , wherein the anti-p-cadherin antibody is a monoclonal antibody, a recombinant antibody, a chimeric antibody, a humanized antibody, or a fragment thereof. 
     
     
         19 : A kit suitable for preparing a radioactive metal-labeled anti-p-cadherin antibody, comprising a metal chelating reagent-binding anti-p-cadherin antibody of  claim 14 . 
     
     
         20 : The kit of  claim 19 , 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 or a chimeric antibody thereof or a humanized antibody thereof, or a fragment of any of these antibodies. 
     
     
         21 : A method for producing a metal-chelating reagent-binding anti-p-cadherin antibody; comprising
 adding an anti-p-cadherin antibody and a metal-chelating reagent at a ratio of 1:0.1 to 1:less than 5 to react.   
     
     
         22 : The method of  claim 21 , wherein the anti-p-cadherin antibody and the metal chelating reagent are added at a ratio of 1:1 to 1:less than 3 to react. 
     
     
         23 : A method for treating a p-cadherin expressing cancer, comprising:
 administering an effective amount of the radioactive metal-labeled anti-p-cadherin antibody of  claim 6  to a subject in need thereof.   
     
     
         24 : A method for diagnosing a p-cadherin expressing cancer, comprising:
 administering an effective amount of the radioactive metal-labeled anti-p-cadherin antibody of  claim 9  to a subject in need thereof; and   diagnosing the p-cadherin expressing cancer.