Colon and pancreas cancer specific antigens and antibodies

Abstract

This invention relates to NPC-1 antigen on the MUC5AC protein and 16C3 antigen on CEACAM5 and CEACAM6 proteins, and 31.1 epitope on the A33 protein are differentially expressed in cancers including, lung cancer, ovarian cancer, pancreas cancer, breast cancer, and colon cancer, and diagnostic and therapeutic usages. Further, NPC-1, 16C3, and/or 31.1 epitope specific antibodies and diagnostic and therapeutic methods of use.

1 . An isolated polypeptide comprising a NPC-1 epitope. 
     
     
         2 . The polypeptide of  claim 1 , wherein the NPC-1 epitope comprises a glycosylation variant (glycotope) expressed by tumor cells, is sensitive to treatment by neuraminidase (α2→3,6,8,9), or is not sensitive to treatment by β-glucosaminidase, O-glycosidase, PNGase F, neuraminidase (α2→3), or f3 (1-4) galactosidase. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The polypeptide of  claim 1 , wherein said NPC-1 epitope is selectively bound by an antibody selected from the group consisting of NPC-1 (NEO-101), NEO-102, and NE0103 or is not selectively bound by an antibody selected from the group consisting of 45M1, H00004586, CLH-2,2-11M1, 9-13M1, 1-13M1, 2-12M1, and H-160. 
     
     
         6 . (canceled) 
     
     
         7 . The polypeptide of  claim 1 , wherein said NPC-1 epitope comprises a peptide comprising residues 1-338, 1-306, 1-289, or 1-151 residues of the tandem repeat region of MUC5AC-long or is not located in a peptide consisting of residues 1-136 or 1-85 residues of the tandem repeat region of MUC5AC-long. 
     
     
         8 . (canceled) 
     
     
         9 . The polypeptide of  claim 1 , wherein said polypeptide comprises an amino acid sequence with at least 80% homology to the amino acid sequence selected from the group consisting of SEQ ID NO: 3, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, 34, 35, 36, and 37. 
     
     
         10 - 25 . (canceled) 
     
     
         26 . A conjugate comprising the polypeptide of  claim 1 , directly or indirectly, conjugated to a cytotoxic agent, a therapeutic agent, label, or an immunosuppressive agent. 
     
     
         27 - 30 . (canceled) 
     
     
         31 . A composition comprising the polypeptide of of  claim 1 , optionally further comprising a pharmaceutically acceptable carrier. 
     
     
         32 - 50 . (canceled) 
     
     
         51 . An isolated antibody that binds to a NPC-1 epitope or an epitope binding fragment thereof, that specifically binds an tumor specific epitope of  claim 1 , wherein said antibody or antibody fragment does not comprise any of the same CDR's as the NPC-1 antibody. 
     
     
         52 . The antibody of  claim 51 , wherein said antibody comprises at least one light chain sequence selected from the group consisting of SEQ ID NO: 52, 62, and 72 or wherein said antibody comprises at least one heavy chain sequence selected from the group consisting of SEQ ID NO: 57, 67, and 74. 
     
     
         53 . (canceled) 
     
     
         54 . The antibody of  claim 51 , wherein said antibody comprises at least one light chain or heavy chain CDR sequence selected from the group consisting of SEQ ID NOs: 53, 54, 55, 58, 59, 60, 63, 64, 65, 68, 69, and 70. 
     
     
         55 - 65 . (canceled) 
     
     
         66 . The antibody of  claim 51 , wherein said fragment is a Fab, Fab′, F(ab′)2, Fv, CDR, paratope, or portion of an antibody that is capable of binding the antigen. 
     
     
         67 . The antibody of  claim 51 , wherein said antibody is chimeric, humanized, anti-idiotypic, single-chain, bifunctional, or co-specific. 
     
     
         68 . The antibody of  claim 51 , wherein said antibody or fragment is directly or indirectly conjugated to a label, cytotoxic agent, therapeutic agent, or an immunosuppressive agent. 
     
     
         69 - 74 . (canceled) 
     
     
         75 . A composition comprising the antibody or antibody fragment of of  claim 51 . 
     
     
         76 - 82 . (canceled) 
     
     
         83 . A method for treating cancer comprising administering an effective amount of an antigen comprising at least one NPC-1 epitope, or antibody or a fragment thereof, that recognizes a NPC-1 epitope to a patient in need thereof, wherein said antibody or fragment does not comprise the same CDRs as the NPC-1 antibody. 
     
     
         84 - 119 . (canceled) 
     
     
         120 . The method of  claim 83 , wherein said antigen or antibody is administered in combination with another antibody, a lymphokine, or a hematopoietic growth factor, optionally wherein said agent is administered simultaneously or sequentially with the antibody. 
     
     
         121 . (canceled) 
     
     
         122 . The method of  claim 83 , wherein said cancer is lung, breast, pancreas, uterine, esophageal, colorectal, or liver cancer. 
     
     
         123 - 128 . (canceled) 
     
     
         129 . A method for detecting a NPC-1 epitope comprising
 (a) contacting a test sample with an antibody, or fragment thereof, that binds a NPC-1 epitope, and   (b) assaying for antibody-epitope complexes,   wherein the presence of said epitope is indicative of a carcinoma and wherein said antibody or fragment does not comprise the same CDRs as the NPC-1 antibody.   
     
     
         130 - 182 . (canceled) 
     
     
         183 . A method for treating cancer comprising administering an effective amount of a composition comprising at least two of the following:
 (a) an antibody, or a fragment thereof, that binds a NPC-1 epitope;   (b) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and   (c) an antibody, or a fragment thereof, that recognizes an 31.1 epitope to a patient in need thereof,   optionally, wherein said composition comprises three of said antibodies.   
     
     
         184 - 188 . (canceled) 
     
     
         189 . A method for detecting a tumor-associated NPC-1 epitope comprising
 (a) contacting a test sample with a composition comprising at least two of the following:
 (i) an antibody, or a fragment thereof, that binds a NPC-1 epitope; 
 (ii) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and 
 (iii) an antibody, or a fragment thereof, that recognizes an 31.1 epitope to a patient in need thereof, and 
   (b) assaying for antibody-epitope complexes, wherein the presence of said epitope is indicative of a carcinoma,   optionally, wherein said composition comprises three of said antibodies.   
     
     
         190 - 199 . (canceled)