Anti-ceacam1 recombinant antibodies for cancer therapy

Abstract

Provided herein are recombinant monoclonal antibodies and antigen-binding portions thereof useful in inhibiting CEACAM1 in tumor cells, and methods of their use in anti-tumor proliferation and invasiveness therapies, such as the treatment of cancer, particularly pancreatic cancer.

We claim: 
     
         1 - 28 . (canceled) 
     
     
         29 . An isolated CEACAM1-specific recombinant monoclonal antibody or an antigen-binding portion thereof, comprising: at least one light chain component and at least one heavy chain component, wherein said heavy chain component comprises the amino acids of SEQ ID NO:26 or 85% identity thereof, SEQ ID NO:28 or 85% identity thereof, or SEQ ID NO:30 or 85% identity thereof; and said light chain component comprises the amino acids of SEQ ID NO:27 or 85% identity thereof, SEQ ID NO:29 or 85% identity thereof, SEQ ID NO:31 or 85% identity thereof or SEQ ID NO:32 or 85% identity thereof, and wherein said antibody or an antigen-binding portion thereof binds the antigen recognized by the monocloncal antibody 5F4, 34B1, or 26H7. 
     
     
         30 . The isolated CEACAM1-specific recombinant monoclonal antibody or an antigen binding portion thereof of  claim 29 , wherein the anti-CEACAM1-specific recombinant monoclonal antibody is a humanized antibody or portion thereof. 
     
     
         31 . The isolated CEACAM1-specific recombinant monoclonal antibody or an antigen binding portion thereof of  claim 29 , wherein the anti-CEACAM1-specific recombinant monoclonal antibody is an affinity-matured antibody or portion thereof. 
     
     
         32 . The isolated CEACAM1-specific recombinant monoclonal antibody or an antigen-binding portion thereof of  claim 29 , wherein the antibody portion is a Fab fragment, a Fab′ fragment, a Fd fragment, a Fd′ fragment, a Fv fragment, a dAb fragment, a F(ab′) 2  fragment, a single chain fragment, a diabody, or a linear antibody. 
     
     
         33 . The antibody or antigen-binding portion thereof of  claim 29 , wherein said antibody is linked to a label. 
     
     
         34 . The isolated CEACAM1-specific recombinant monoclonal antibody or an antigen-binding portion thereof of  claim 29 , further comprising an agent conjugated to the anti-CEACAM1 recombinant antibody or portion thereof to form an immunoconjugate specific for CEACAM1. 
     
     
         35 . The isolated CEACAM1-specific recombinant monoclonal antibody or an antigen-binding portion thereof of  claim 34 , wherein the agent conjugated to the antibody or antibody fragment thereof is a chemotherapeutic agent, a toxin, a radioactive isotope, a small molecule, an siRNA, a nanoparticle, or a microbubble. 
     
     
         36 . A method of treating cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an isolated recombinant antibody or antigen-binding portion thereof comprising: at least one light chain component and at least one heavy chain component, wherein said heavy chain component comprises the amino acids of SEQ ID NO:26 or 85% identity thereof, SEQ ID NO:28 or 85% identity thereof, or SEQ ID NO:30 or 85% identity thereof; and said light chain component comprises the amino acids of SEQ ID NO:27 or 85% identity thereof, SEQ ID NO:29 or 85% identity thereof, SEQ ID NO:31 or 85% identity thereof or SEQ ID NO:32 or 85% identity thereof, and wherein said antibody or an antigen-binding portion thereof binds the antigen recognized by the monocloncal antibody 5F4, 34B1, or 26H7. 
     
     
         36 . The method of  claim 36 , wherein the method further comprises the administration of one or more chemotherapeutic agents, angiogenesis inhibitors, cytotoxic agents, or anti-proliferative agents. 
     
     
         37 . The method of  claim 36 , wherein the cancer is melanoma. 
     
     
         38 . The method of  claim 36 , wherein the cancer is colorectal.