High affinity humanized anti-CEA monoclonal antibodies

Abstract

Novel humanized monoclonal antibodies, fragments or derivatives thereof which specifically bind carcinoembryonic antigen (CEA) are provided as well as methods for their manufacture. These humanized antibodies are useful in the treatment of cancers which express CEA as well as for diagnostic purposes, e.g., for in vivo imaging of tumors or cancer cells which express CEA.

What is claimed is:  
     
         1 . A humanized antibody or humanized antibody fragment which specifically binds CEA wherein said humanized antibody or humanized antibody fragment is derived from a murine antibody that binds CEA.  
     
     
         2 . The humanized antibody or humanized antibody fragment of  claim 1  comprising CDRs which are obtained from said murine antibody, and comprising VH FRs which have an amino acid sequence of the NEWM FRs or the humanized COL-1 FRs of FIG. 1 or  13 , and comprising VL FRs which have an amino acid sequence of the REI FRs or the humanized COL-1 FRs of FIG. 2 or  14 .  
     
     
         3 . The humanized antibody or humanized antibody fragment of  claim 2  wherein said humanized antibody has an antigen binding affinity for CEA which is at least 10% that of COL-1 and said humanized antibody fragment has an amino acid sequence identical to that of a constituent part of said humanized antibody.  
     
     
         4 . The humanized antibody or humanized antibody fragment of  claim 2  wherein said humanized antibody has an antigen binding affinity for CEA which is at least 30% that of COL-1.  
     
     
         5 . The humanized antibody or humanized antibody fragment of  claim 2  wherein said murine antibody is any one of COL-1 through COL-15.  
     
     
         6 . The humanized antibody or humanized antibody fragment of  claim 5  wherein said murine antibody is COL-1.  
     
     
         7 . The humanized antibody or humanized antibody fragment of  claim 6  wherein said humanized antibody is expressed by ATCC CRL-12208 and said humanized antibody fragment has an amino acid sequence identical to that of a constituent part of the antibody expressed by ATCC CRL-12208.  
     
     
         8 . The humanized antibody or humanized antibody fragment of  claim 1  comprising a humanized variable heavy chain sequence of FIG. 1 or  13  or a humanized variable light chain sequence of FIG. 2 or  14 , or comprising both said humanized variable heavy chain sequence and said humanized variable light chain sequence.  
     
     
         9 . A nucleic acid sequence from which may be expressed a humanized antibody or humanized antibody fragment according to  claim 2 .  
     
     
         10 . A vector comprising a nucleic acid sequence according to  claim 9 .  
     
     
         11 . The vector according to  claim 10  wherein said vector is a bare nucleic acid segment, a carrier-associated nucleic acid segment, a nucleoprotein, a plasmid, a virus, a viroid, or a transposable element.  
     
     
         12 . A composition suitable for the treatment of cancer in that it comprises a therapeutically effective amount of a humanized antibody or humanized antibody fragment according to  claim 1 .  
     
     
         13 . The composition of  claim 12  wherein said humanized antibody or humanized antibody fragment is, directly or indirectly, associated with or linked to an effector moiety having therapeutic activity, and the composition is suitable for the treatment of cancer.  
     
     
         14 . The composition of  claim 13  wherein said effector moiety is a radionuclide, therapeutic enzyme, anti-cancer drug, cytokine, cytotoxin, or anti-proliferative agent.  
     
     
         15 . A composition suitable for the in vivo or in vitro detection of cancer characterized in that it comprises a diagnostically effective amount of a humanized antibody or humanized antibody fragment according to  claim 1 .  
     
     
         16 . The composition of  claim 15  wherein said humanized antibody or humanized antibody fragment is, directly or indirectly, associated with or linked to a detectable label, and the composition is suitable for detection of cancer.  
     
     
         17 . The composition of  claim 16  wherein the detectable label is a radionuclide or an enzyme.  
     
     
         18 . A method for in vivo treatment of a mammal having a CEA-expressing cancer comprising a step of administering to the mammal a therapeutically effective amount of a composition according to  claim 12 .  
     
     
         19 . A method of in vitro immunodetection of CEA-expressing cancer cells comprising a step of contacting the cancer cells with a composition according to  claim 15 .  
     
     
         20 . The method of  claim 19  wherein the humanized antibodies or humanized antibody fragments of the composition are bound to a solid support.  
     
     
         21 . A method of in vivo immunodetection of CEA-expressing cancer cells in a mammal comprising a step of administering to the mammal a diagnostically effective amount of a composition according to  claim 15 .  
     
     
         22 . The method of  claim 20  wherein said immunodetection is in vivo tumor imaging.  
     
     
         23 . A method of in vivo treatment of cancer comprising the steps of (i) intravenously administering a radionuclide-labeled antibody, (ii) thereafter detecting tumor cells using a radionuclide activity probe, and (iii) thereafter removing the detected tumor cells by surgical excision, characterized in that the antibody is a humanized antibody or humanized antibody fragment according to  claim 1 .  
     
     
         24 . The method of  claim 23 , wherein the radionuclide is  125 I or  131 I.