Anti-a33 antibody

Abstract

The present invention provides: an antibody or a antibody fragment thereof, which can bind to A33, which specifically attacks A33-expressing tumor cells with the use of ADCC and CDC based on the immune system, and for which no HAHA is produced; and a preventive or therapeutic agent for various malignant tumors including solid tumors that are currently treated with difficulty, which contains the antibody or an antibody fragment thereof. Specifically, the antibody or a functional fragment thereof is capable of binding to A33 and is produced by a hybridoma M10 (accession No. FERM BP-10107), M96 (accession No. FERM BP-10108), M 165 (accession No. FERM BP-10106), N26 (accession No. FERM BP-10109), Q47 (accession No. FERM BP-10104), Q54 (accession No. FERM BP-10105), or R5 (accession No. FERM BP-10107). The preventive or therapeutic agent for tumors contains the antibody or a functional fragment thereof.

1 . A human antibody or a functional fragment thereof, which binds to A33. 
     
     
         2 . The human antibody or a functional fragment thereof according to  claim 1 , wherein the class of the antibody heavy chain constant region is IgG. 
     
     
         3 . The human antibody or a functional fragment thereof according to  claim 2 , wherein the IgG subclass is IgG1. 
     
     
         4 . The human antibody or a functional fragment thereof according to  claim 1 , which is produced by a hybridoma selected from the group consisting of the following (a) to (f):
 (a) M10 (accession No. FERM BP-10107);   (b) M96 (accession No. FERM BP-10108);   (c) M165 (accession No. FERM BP-10106):   (d) 47 (accession No. FERM BP-10104);   (e) Q54 (accession No. FERM BP-10105); and   (f) R5 (accession No. FERM BP-10103).   
     
     
         5 . The human antibody or a functional fragment thereof according to  claim 1 , which recognizes the same epitope as that recognized by an antibody produced by a hybridoma selected from the group consisting of the following (a) to (f):
 (a) M10 (accession No. FERM BP-10107);   (b) M96 (accession No. FERM BP-10108);   (c) M165 (accession No. FERM BP-10106):   (d) 47 (accession No. FERM BP-10104);   (e) Q54 (accession No. FERM BP-10105); and   (f) R5 (accession No. FERM BP-10103).   
     
     
         6 . The human antibody or a functional fragment thereof according to  claim 1 , which has the heavy chain variable region and the light chain variable region of an antibody produced by a hybridoma selected from the group consisting of the following (a) to (f):
 (a) M10 (accession No. FERM BP-10107);   (b) M96 (accession No. FERM BP-10108);   (c) M165 (accession No. FERM BP-10106):   (d) 47 (accession No. FERM BP-10104);   (e) Q54 (accession No. FERM BP-10105); and   (f) R5 (accession No. FERM BP-10103).   
     
     
         7 . The human antibody or a functional fragment thereof according to  claim 1 , which has a heavy chain variable region and a light chain variable region selected from the group consisting of the following (g) to (m):
 (g) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 23 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 25;   (h) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 27 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 29;   (i) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 31 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 33;   (j) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 35 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 37;   (k) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 43 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 45;   (l) the variable region of the heavy chain amino acid sequence represented by SEQ ID NO: 47 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 49; and   (m) the variable region of the heavy chain amino acid sequence represented by SEQ ID 51 and the variable region of the light chain amino acid sequence represented by SEQ ID NO: 53.   
     
     
         8 . A pharmaceutical composition, which contains the human antibody or the functional fragment thereof according to  claim 1  as an active ingredient. 
     
     
         9 . A preventive or therapeutic agent for a tumor, which contains the human antibody or the functional fragment thereof according to  claim 1  as an active ingredient. 
     
     
         10 . The preventive or therapeutic agent for a tumor according to  claim 9 , wherein the tumor is a tumor containing cancer cells expressing A33. 
     
     
         11 . The preventive or therapeutic agent for a tumor according to  claim 9 , wherein the tumor is selected from the group consisting of colorectal cancer, colon cancer, rectal cancer, gastric cancer, pancreatic cancer, breast cancer, melanoma, renal cell cancer, cervical cancer, endometrial cancer, ovarian cancer, esophageal cancer, prostatic cancer, testicular cancer, and mesothelial cancer. 
     
     
         12 . A hybridoma, which is selected from the group consisting of the following (a) to (f):
 (a) M10 (accession No. FERM BP-10107);   (b) M96 (accession No. FERM BP-10108);   (c) M165 (accession No. FERM BP-10106):   (d) 47 (accession No. FERM BP-10104);   (e) Q54 (accession No. FERM BP-10105); and   (f) R5 (accession No. FERM BP-10103).   
     
     
         13 . A method for producing an antibody, which comprises culturing the hybridoma according to  claim 12  and then obtaining the antibody from the culture product. 
     
     
         14 . A method for producing an antibody, which comprises isolating a gene encoding an antibody that binds to A33 from the hybridoma according to  claim 12 , constructing an expression vector having the gene, introducing the expression vector into a host, culturing the host, and then obtaining the antibody from the culture product. 
     
     
         15 . A method for producing an antibody, which comprises isolating genes encoding the heavy chain variable region and the light chain variable region of an antibody that binds to A33 from the hybridoma according to  claim 12 , constructing an expression vector having the genes, introducing the expression vector into a host, culturing the host, and then obtaining the antibody from the culture product. 
     
     
         16 . A method for producing an antibody, which comprises constructing an expression vector having a heavy chain variable region and a light chain variable region selected from the group consisting of the following (n) to (u), introducing the expression vector into a host, culturing the host, and then obtaining the antibody from the culture product:
 (n) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 22 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 24;   (o) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 26 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 28;   (p) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 30 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 32;   (q) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 34 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 36;   (r) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 38 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 40;   (s) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 42 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 44;   (t) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 46 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 48; and   (u) the variable region of the heavy chain nucleic acid sequence represented by SEQ ID NO: 50 and the variable region of the light chain nucleic acid sequence represented by SEQ ID NO: 52.   
     
     
         17 . The method according to  claims 13  to  16 , wherein the host is selected from the group consisting of  Escherichia coli , a yeast cell, an insect cell, a mammalian cell, a plant cell, a plant, and a mammal.