Nucleotide and protein sequences of an antibody directed against an epitope common to human acidic and basic ferritins, monoclonal antibodies or antibody-like molecules comprising these sequences and use thereof

Abstract

The present invention is directed to monoclonal, chimeric or humanized, antibodies or antibody-like molecules that recognize an epitope common to human acidic and basic isoferritins. The anti-ferritin antibodies or antibody-like molecules can be used in pharmaceutical compositions for immunotherapy or radioimmunotherapy to target various cancer cells in a mammal. A method for delivering anti-ferritin antibodies or antibody-like molecules to cancerous lymph cells, pancreatic cells, lymphatic endothelium cells, and liver cells is also disclosed, as well as methods for treating pancreatic cancer, hepatocellular carcinomas, Kaposi's sarcoma and Hodgkin's lymphoma.

1 - 50 . (canceled) 
     
     
         51 . A method of delivering a drug, radioactive material, toxin, immune killer cell or a combination thereof to cells containing basic and acidic ferritin, said method comprising administering a pharmaceutical composition comprising
 a) a chimeric anti-ferritin monoclonal antibody or a fragment thereof that binds both human acidic and basic ferritin, wherein the antibody comprises:
 (i) two light chains, each consisting of a polypeptide comprising SEQ ID NO:2 or a variant having a degree of similarity of at least 90% with SEQ ID NO:2 wherein the CDR1, CDR2 and CDR3 domains of said variant consist respectively of SEQ ID NO:20, SEQ ID NO:22 and SEQ ID NO:24; and 
 (ii) two heavy chains, each consisting of a polypeptide comprising SEQ ID NO:4 or a variant having a degree of similarity of at least 90% with SEQ ID NO:4 wherein the CDR1, CDR2 and CDR3 domains of said variant consist respectively of SEQ ID NO:30, SEQ ID NO:28 and SEQ ID NO: 26; and    
   b) a drug, radioactive material, roxin, immune killer cell or a combination thereof,   thereby delivering said drug, radioactive material, toxin, immune killer cell or a combination thereof to cells containing acidic or basic ferritin.   
     
     
         52 . A method of delivering a drug to cells containing basic and acidic ferritin, said method comprising administering a pharmaceutical composition comprising a) a chimeric anti-ferritin monoclonal antibody or a fragment thereof that binds both human acidic and basic ferritin, wherein the antibody comprises two light chains comprising SEQ ID NO:2 and two heavy chains comprising SEQ ID NO:4 and b) said drug; and c) a pharmaceutically acceptable carrier. 
     
     
         53 - 88 . (canceled) 
     
     
         89 . The method of  claim 52 , wherein said light chains each consist of SEQ ID NO:2 and said heavy chains each consist of SEQ ID NO:4. 
     
     
         90 . The method of  claim 51  wherein the fragment is a Fv fragment, a Fab fragment, a bispecific monoclonal antibody, a trispecific monoclonal antibody, a bifunctional antibody, a say molecule, a Bis-scFv or a diabody. 
     
     
         91 . The method of  claim 51  wherein the monoclonal antibody or fragment thereof is attached to the drug, radioactive material, toxin, immune killer cell or combination thereof. 
     
     
         92 . The method of  claim 51 , wherein said radioisotope is selected from the group consisting of alpha-, beta-, gamma-, beta- gamma- and alpha-beta-emitting radioisotopes. 
     
     
         93 . The method of  claim 51  wherein said radioisotope is conjugated through a chelating agent conjugated to said antibody. 
     
     
         94 . The method of  claim 93  wherein said chelating agent is selected from the group consisting of diethylenetriaminepentaacetic acid (DTPA); 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); 1,3-bis[N4N-(2-aminoethyl)-2-aminoethyl]-propane-N,N,N ,N′,N″,N′″,N″″,N″″′-octaacetic acid (LiLo); N-(S-acetylmercaptoacetyl)(p-NCS) phenylalanylglycylglycine ethyl ester; 5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane; 1,4,7,10-tetraazacyclotridecane-N,N,N′,N″,N′″-tetra-acetic acid (TRITA); 1,4,8,11-tetraaxacyclootetra-decane-N, N\N″, N′″-tetraacetic acid (TETA); and
 1,5,9,13-tetraazacyclohexa decane-N,N′,N″“,N”“”-tetraacctic acid. 
 
     
     
         95 . The method of  claim 51  wherein said drug is a pyrimidine drug. 
     
     
         96 . The method of  claim 95  wherein said pyrimidine drug is selected from the group consisting of fluorouracil, capecitabine, cytarabine, floxuridine and gemcitabine. 
     
     
         97 . The method of  claim 52  wherein the fragment is a Fv fragment, a Fab fragment, a bispecific monoclonal antibody, a trispecific monoclonal antibody, a bifunctional antibody, a scFv molecule, a Bis-scFv or a diabody. 
     
     
         98 . The method of  claim 52  wherein the monoclonal antibody or fragment thereof is attached to the drug. 
     
     
         99 . The method of  claim 52  wherein said drug is a pyrimidine drug. 
     
     
         100 . The method of  claim 99  wherein said pyrimidine drug is selected from the group consisting of fluorouracil, capecitabine, cytarabine, floxuridine and gemcitabine. 
     
     
         101 . The method of  claim 51  wherein the delivering is used to treat pancreatic cancer, Hodgkin's lymphoma, Kaposi's sarcoma or hepatocellular carcinoma. 
     
     
         102 . The method of  claim 52  wherein the delivering is used to treat pancreatic cancer, Hodgkin's lymphoma, Kaposi's sarcoma or hepatocellular carcinoma.