Compositions and methods for diagnosing and treating cancer

Abstract

An isolated antibody that specifically binds to an extracellular domain of two or more human FZD receptors and inhibits growth of tumor cells is described. Also described is a method of treating cancer comprising administering an antibody of the present disclosure in an amount effective to inhibit tumor cell growth.

1 . An isolated polynucleotide encoding an antibody that specifically binds to an extracellular domain of two or more human FZD receptors and inhibits growth of tumor cells. 
     
     
         2 - 14 . (canceled) 
     
     
         15 . A method of treating cancer, the method comprising administering to a subject in need thereof a monoclonal antibody in an amount effective to inhibit tumor cell growth, wherein the monoclonal antibody comprises an antigen binding site that specifically binds to the extracellular domains of human FZD5 and FZD8, wherein the extracellular domain of human FZD5 comprises approximately amino acid 27 to 233 of SEQ ID NO:3, and the extracellular domain of human FZD8 comprises approximately amino acid 28 to 158 of SEQ ID NO:6. 
     
     
         16 . The method of  claim 15  wherein the antibody is conjugated to a cytotoxic moiety. 
     
     
         17 . The method of  claim 15  further comprising administering at least one additional therapeutic agent appropriate for effecting combination therapy. 
     
     
         18 . The method of  claim 15  wherein the tumor cells are chosen from a breast tumor, colorectal tumor, lung tumor, pancreatic tumor, prostate tumor, and a head and neck tumor. 
     
     
         19 . The method of  claim 17 , wherein the at least one additional therapeutic agent is a chemotherapeutic agent. 
     
     
         20 . The method of  claim 15 , wherein the antibody is a chimeric antibody. 
     
     
         21 . The method of  claim 15 , wherein the antibody is a humanized antibody. 
     
     
         22 . The method of  claim 15 , wherein the antibody is a human antibody. 
     
     
         23 . The method of  claim 15 , wherein the antibody is an intact antibody. 
     
     
         24 . The method of  claim 15 , wherein the antigen binding site binds to the extracellular domains of human FZD5 and FZD8 at a site comprising amino acid residues that are identical between the extracellular domains of human FZD5 and FZD8. 
     
     
         25 . The method of  claim 24 , wherein the antigen binding site binds to the extracellular domains of human FZD5 and FZD8 at a site comprising at least 3 amino acid residues that are identical between the extracellular domains of human FZD5 and FZD8. 
     
     
         26 . The method of  claim 24 , wherein the amino acid residues that are identical between the extracellular domains of human FZD5 and FZD8 are contiguous. 
     
     
         27 . The method of  claim 25 , wherein the at least 3 amino acid residues that are identical between the extracellular domains of human FZD5 and FZD8 are contiguous. 
     
     
         27 . A method of inhibiting the growth of tumor cells comprising contacting the tumor cells with an effective amount of a monoclonal antibody that comprises an antigen binding site that specifically binds to the extracellular domains of human FZD5 and FZD8, wherein the extracellular domain of human FZD5 comprises approximately amino acid 27 to 233 of SEQ ID NO:3, and the extracellular domain of human FZD8 comprises approximately amino acid 28 to 158 of SEQ ID NO:6. 
     
     
         28 . The method of  claim 27  wherein the tumor cells are chosen from a breast tumor, colorectal tumor, lung tumor, pancreatic tumor, prostate tumor, and a head and neck tumor. 
     
     
         29 . The method of  claim 27 , wherein the antibody is a chimeric antibody. 
     
     
         30 . The method of  claim 27 , wherein the antibody is a humanized antibody. 
     
     
         31 . The method of  claim 27 , wherein the antibody is a human antibody. 
     
     
         32 . The method of  claim 27 , wherein the antibody is an intact antibody. 
     
     
         33 . The method of  claim 27 , wherein the antigen binding site binds to the extracellular domains of human FZD5 and FZD8 at a site comprising amino acid residues that are identical between the extracellular domains of human FZD5 and FZD8.