Compositions and Methods for Diagnosing and Treating Cancer

Abstract

An isolated antibody that specifically binds to an extracellular domain of human DLL4 and affects growth of a tumor comprising cancer stem cells is described. Also described is a method of treating cancer comprising administering a therapeutically effective amount of an anti-DLL4 antibody.

1 - 64 . (canceled) 
     
     
         65 . A method of inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds human delta-like ligand 4 (DLL4), wherein the antibody binds the same epitope as that of antibody 21M18 produced by the hybridoma deposited with ATCC having deposit no. PTA-8670. 
     
     
         66 . The method of  claim 65 , wherein the antibody is an antibody fragment. 
     
     
         67 . The method of  claim 65 , wherein the antibody is a monoclonal antibody. 
     
     
         68 . The method of  claim 67 , wherein the antibody is a chimeric, bispecific, human, or humanized antibody. 
     
     
         69 . The method of  claim 68 , wherein the antibody is a humanized antibody. 
     
     
         70 . The method of  claim 67 , wherein the monoclonal antibody is an antibody fragment. 
     
     
         71 . The method of  claim 67 , wherein the antibody is an IgG antibody. 
     
     
         72 . The method of  claim 71 , wherein the antibody is an IgG 2  antibody. 
     
     
         73 . The method of  claim 71 , wherein the antibody is an IgG 1  antibody. 
     
     
         74 . The method of  claim 67 , wherein the tumor is a colorectal tumor, a breast tumor, lung tumor, an ovarian tumor, a liver tumor, a prostate tumor, a kidney tumor, or a pancreatic tumor. 
     
     
         75 . The method of  claim 74 , wherein the tumor is a lung tumor. 
     
     
         76 . The method of  claim 75 , wherein the lung tumor is non-small cell lung tumor. 
     
     
         77 . The method of  claim 74 , wherein the tumor is a pancreatic tumor. 
     
     
         78 . The method of  claim 77 , where the pancreatic tumor is metastatic. 
     
     
         79 . The method of  claim 74 , wherein the tumor is an ovarian tumor. 
     
     
         80 . The method of  claim 74 , wherein the tumor is a breast tumor. 
     
     
         81 . The method of  claim 67 , further comprising administering a second therapeutic agent to the subject. 
     
     
         82 . The method of  claim 81 , wherein the second therapeutic agent is a chemotherapeutic agent. 
     
     
         83 . The method of  claim 81 , wherein the second therapeutic agent is a second therapeutic antibody. 
     
     
         84 . The method of  claim 81 , wherein the second therapeutic agent is radiation therapy. 
     
     
         85 . A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds human delta-like ligand 4 (DLL4), wherein the antibody binds the same epitope as that of antibody 21M18 produced by the hybridoma deposited with ATCC having deposit no. PTA-8670. 
     
     
         86 . The method of  claim 85 , wherein the antibody is an antibody fragment. 
     
     
         87 . The method of  claim 85 , wherein the antibody is a monoclonal antibody. 
     
     
         88 . The method of  claim 87 , wherein the antibody is a chimeric, bispecific, human, or humanized antibody. 
     
     
         89 . The method of  claim 88 , wherein the antibody is a humanized antibody. 
     
     
         90 . The method of  claim 87 , wherein the monoclonal antibody is an antibody fragment. 
     
     
         91 . The method of  claim 87 , wherein the antibody is an IgG antibody. 
     
     
         92 . The method of  claim 91 , wherein the antibody is an IgG 2  antibody. 
     
     
         93 . The method of  claim 91 , wherein the antibody is an IgG 1  antibody. 
     
     
         94 . The method of  claim 87 , wherein the cancer is colorectal cancer, breast cancer, lung cancer, ovarian cancer, liver cancer, prostate cancer, kidney cancer, or pancreatic cancer. 
     
     
         95 . The method of  claim 94 , wherein the cancer is lung cancer. 
     
     
         96 . The method of  claim 95 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         97 . The method of  claim 94 , wherein the cancer is pancreatic cancer. 
     
     
         98 . The method of  claim 97 , where the pancreatic cancer is metastatic. 
     
     
         99 . The method of  claim 94 , wherein the cancer is ovarian cancer. 
     
     
         100 . The method of  claim 94 , wherein the cancer is breast cancer. 
     
     
         101 . The method of  claim 87 , further comprising administering a second therapeutic agent to the subject. 
     
     
         102 . The method of  claim 101 , wherein the second therapeutic agent is a chemotherapeutic agent. 
     
     
         103 . The method of  claim 101 , wherein the second therapeutic agent is a second therapeutic antibody. 
     
     
         104 . The method of  claim 101 , wherein the second therapeutic agent is radiation therapy.