Antibodies recognizing a carbohydrate containing epitope on cd-43 and cea expressed on cancer cells and methods using same

Abstract

The present invention provides novel antibodies specifically bind to an epitope on CD43 and CEA expressed on nonhematopoietic cancer cells, but do not specifically bind to a CD43 expressed by a leukocyte or by a Jurkat cell, and is capable of inducing apoptosis of the nonhematopoietic cancer cell after binding to the epitope on cell surface of the nonhematopoietic cancer cell in the absence of cytotoxin conjugation and immune effector function, wherein the epitope comprises a carbohydrate structure and the binding of the antibody to the epitope is inhibited by a carbohydrate comprising a Le a structure, a Le a -lactose structure, a LNDFH II structure, or a LNT structure. In addition, the present invention also provides use of the antibodies described herein for diagnostic and therapeutic purposes.

1 - 34 . (canceled) 
     
     
         35 : A method for diagnosing a nonhematopoietic cancer in an individual suspected of having cancer comprising contacting a sample from the individual with a monoclonal antibody; wherein the monoclonal antibody binds to an epitope on the extracellular domain of a human CD43 or a human CEA expressed by nonhematopoietic cancer cells, but does not specifically bind to a human CD43 expressed on the cell surface of human peripheral T cells or Jurkat cells, and wherein epitope comprises a carbohydrate and the binding of the antibody to the epitope is inhibited by oligosaccharides Le a , Le a -lactose, and Lacto-N-difucohexaose II (LNDFH II); and wherein the presence of binding between the antibody and a cell in the sample indicates that the sample may contain a cancer cell. 
     
     
         36 : The method of  claim 35 , wherein the epitope comprises a fucose. 
     
     
         37 : The method of  claim 35 , wherein the binding of the antibody to the epitope is inhibited by oligosaccharide LNT. 
     
     
         38 : The method of  claim 35 , wherein the monoclonal antibody competes for binding to nonhematopoietic cancer cells with an antibody comprising a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO: 1, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:2. 
     
     
         39 : The method of  claim 35 , wherein the monoclonal antibody competes for binding to nonhematopoietic cancer cells with an antibody comprising a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:4. 
     
     
         40 : The method of  claim 35 , wherein the monoclonal antibody competes for binding to nonhematopoietic cancer cells with an antibody comprising a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:5, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:6. 
     
     
         41 : The method of  claim 35 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO: 1, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:2. 
     
     
         42 : The method of  claim 41 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO: 1, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:2. 
     
     
         43 : The method of  claim 35 , wherein the monoclonal antibody comprises a heavy chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:3, and a light chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:4. 
     
     
         44 : The method of  claim 43 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:3, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:4. 
     
     
         45 : The method of  claim 35 , wherein the monoclonal antibody comprises the three CDRs from the amino acid sequence of SEQ ID NO:5, and the light chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:6. 
     
     
         46 : The method of  claim 45 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:5, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:6. 
     
     
         47 : The method of  claim 35 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:7, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:8. 
     
     
         48 : The method of  claim 35 , wherein the nonhematopoietic cancer cell is a human colorectal cancer cell, a human pancreatic cancer cell, a human gastric cancer cell, a human ovarian cancer cell, a human esophageal cancer cell, or a human endometrial cancer cell. 
     
     
         49 : The method of  claim 35 , wherein the monoclonal antibody is a humanized antibody. 
     
     
         50 : The method of  claim 35 , wherein the monoclonal antibody is a chimeric antibody. 
     
     
         51 : The method of  claim 35 , wherein the monoclonal antibody is a human antibody. 
     
     
         52 : The method of  claim 35 , wherein the monoclonal antibody is conjugated to a label. 
     
     
         53 : The method of  claim 52 , wherein the label is selected from the group consisting of an enzyme, a fluorescent molecule, a chemiluminescent molecule, a radioactive molecule, and biotin. 
     
     
         54 : The method of  claim 53 , wherein the label is selected from the group consisting of  3 H,  14 C,  15 N,  35 S,  90 Y,  99 Tc,  111 In,  125 I,  131 I, fluorescein isothocyanate (FITC), rhodamine, lanthanide phosphors, phycoerythrin (PE), horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase, glucose oxidase, glucose-6-phosphate dehydrogenase, alcohol dehyrogenase, malate dehyrogenase, penicillinase, and luciferase. 
     
     
         55 : The method of  claim 35 , wherein the nonhematopoietic cancer is colorectal cancer, pancreatic cancer, gastric cancer, ovarian cancer, esophageal cancer, or endometrial cancer. 
     
     
         56 : A method to determine if an individual suspected of having cancer may be treated with a monoclonal antibody that binds to an epitope on the extracellular domain of a human CD43 or a human CEA expressed by nonhematopoietic cancer cells, but does not specifically bind to a human CD43 expressed on the cell surface of human peripheral T cells or Jurkat cells, wherein epitope comprises a carbohydrate and the binding of the antibody to the epitope is inhibited by oligosaccharides Le a , Le a -lactose, and Lacto-N-difucohexaose II (LNDFH II),
 the method comprising contacting a sample from the individual with a monoclonal antibody; wherein the monoclonal antibody binds to an epitope on the extracellular domain of a human CD43 or a human CEA expressed by nonhematopoietic cancer cells, but does not specifically bind to a human CD43 expressed on the cell surface of human peripheral T cells or Jurkat cells, and wherein epitope comprises a carbohydrate and the binding of the antibody to the epitope is inhibited by oligosaccharides Le a , Le a -lactose, and Lacto-N-difucohexaose II (LNDFH II);   wherein the presence of binding between the antibody and a cell in the sample indicates that the individual having cancer may be treated with the antibody.   
     
     
         57 : A kit for use in diagnosing a nonhematopoietic cancer in an individual comprising a monoclonal antibody which specifically binds to an epitope on the extracellular domain of a human CD43 or CEA expressed by human nonhematopoietic cancer cells but does not specifically bind to a human CD43 expressed on the cell surface of human peripheral T cells or Jurkat cells, wherein epitope comprises a carbohydrate and the binding of the antibody to the epitope is inhibited by oligosaccharides Le a , Le a -lactose, and Lacto-N-difucohexaose II (LNDFH II). 
     
     
         58 : The kit of  claim 57 , wherein the epitope comprises a fucose. 
     
     
         59 : The kit of  claim 57 , wherein the binding of the antibody to the epitope is inhibited by oligosaccharide LNT. 
     
     
         60 : The kit of  claim 57 , wherein the monoclonal antibody competes for binding human nonhematopoietic cancer cells with an antibody comprising a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO: 1, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:2. 
     
     
         61 : The kit of  claim 57 , wherein the monoclonal antibody competes for binding human nonhematopoietic cancer cells with an antibody comprising a heavy chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:5, and a light chain variable region comprising the three CDRs from the amino acid sequence of SEQ ID NO:6. 
     
     
         62 : The kit of  claim 57 , wherein the monoclonal antibody comprises a heavy chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO: 1, and a light chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:2. 
     
     
         63 : The kit of  claim 62 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO: 1, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:2. 
     
     
         64 : The kit of  claim 57 , wherein the monoclonal antibody comprises a heavy chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:3, and a light chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:4. 
     
     
         65 : The kit of  claim 64 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:3, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:4. 
     
     
         66 : The kit of  claim 57 , wherein the monoclonal antibody comprises the three CDRs from the amino acid sequence of SEQ ID NO:5, and the light chain variable region sequence comprising the three CDRs from the amino acid sequence of SEQ ID NO:6. 
     
     
         67 : The kit of  claim 66 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:5, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:6. 
     
     
         68 : The kit of  claim 57 , wherein the monoclonal antibody comprises the heavy chain variable region sequence from the amino acid sequence of SEQ ID NO:7, and the light chain variable region sequence from the amino acid sequence of SEQ ID NO:8. 
     
     
         69 : The kit of claim of  claim 57 , wherein the nonhematopoietic cancer cell is a human colorectal cancer cell, a human pancreatic cancer cell, a human gastric cancer cell, a human ovarian cancer cell, a human esophageal cancer cell, or a human endometrial cancer cell. 
     
     
         70 : The kit of  claim 57 , wherein the monoclonal antibody is a humanized antibody. 
     
     
         71 : The kit of  claim 57 , wherein the monoclonal antibody is a chimeric antibody. 
     
     
         72 : The kit of  claim 57 , wherein the monoclonal antibody is a human antibody. 
     
     
         73 : The kit of  claim 57 , wherein the monoclonal antibody is conjugated to a label. 
     
     
         74 : The kit of  claim 73 , wherein the label is selected from the group consisting of an enzyme, a fluorescent molecule, a chemiluminescent molecule, a radioactive molecule, and biotin. 
     
     
         75 : The kit of  claim 74 , wherein the label is selected from the group consisting of  3 H,  14 C,  15 N,  35 S,  90 Y,  99 Tc,  111 In,  125 I,  131 I, fluorescein isothocyanate (FITC), rhodamine, lanthanide phosphors, phycoerythrin (PE), horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase, glucose oxidase, glucose-6-phosphate dehydrogenase, alcohol dehyrogenase, malate dehyrogenase, penicillinase, and luciferase.