Anticancer agent

Abstract

According to the present invention, an anticancer agent is provided that has as an active ingredient thereof a human antibody light chain that demonstrates cytotoxicity against cancer cells and particularly lung cancer cells. The anticancer agent of the present invention primarily comprises: a human antibody κ-type light chain in the form of a dimer in which the variable region is composed of a polypeptide represented by the amino acid sequence of SEQ ID NO: 1, 9 or 13 or an amino acid sequence in which one or a plurality of amino acids have been added, deleted or substituted in these amino acid sequences; or, a human antibody κ-type light chain in the form of a monomer in which the variable region is composed of a polypeptide represented by the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence in which one or a plurality of amino acids have been added, deleted or substituted in the amino acid sequence.

1 . An anticancer composition, comprising:
 (1) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 1, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (2) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 7, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (3) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 9, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (4) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 13, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (5) a human antibody κ-type light chain in the form of a monomer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 19, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (6) a human antibody κ-type light chain in the form of a monomer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 113th amino acids of SEQ ID NO: 38, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (7) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 112th amino acids of SEQ ID NO: 40, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence; or   (8) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 107th amino acids of SEQ ID NO: 41, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence; and   at least one selected from the group consisting of a pharmaceutically acceptable carrier, diluent and vehicle.   
     
     
         2 . The anticancer composition according to  claim 1 , wherein
 the human antibody κ-type light chain of (1) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 2, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (2) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 8, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (3) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 10, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (4) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 14, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (5) above is a human antibody κ-type light chain in the form of a monomer composed of a polypeptide represented by an amino acid sequence in which cysteine at position 219 has been deleted or substituted by an amino acid other than cysteine in the amino acid sequence of SEQ ID NO: 20, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (6) above is a human antibody κ-type light chain in the form of a monomer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 38, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (7) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by the amino acid sequence of SEQ ID NO: 40, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence; or   the human antibody κ-type light chain of (8) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 41, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence.   
     
     
         3 . The anticancer composition according to  claim 1 , wherein the anticancer composition is in a form which enables the anticancer composition to be delivered to pneumocytes from a nose or bronchi. 
     
     
         4 . The anticancer composition according to  claim 1 , wherein protein contained in the anticancer composition is a dose of 0.01 mg/kg to 30 mg/kg of body weight. 
     
     
         5 . A method of eradicating cancer cells or suppressing or inhibiting a proliferation of the cancer cells, comprising:
 administering a therapeutically effective amount of an anticancer composition to an object requiring an administration, the anticancer composition comprising:   (1) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 1, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (2) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 7, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (3) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 9, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (4) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 13, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (5) a human antibody κ-type light chain in the form of a monomer in which a variable region is composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 19, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (6) a human antibody κ-type light chain in the form of a monomer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 113th amino acids of SEQ ID NO: 38, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   (7) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 112th amino acids of SEQ ID NO: 40, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence; or   (8) a human antibody κ-type light chain in the form of a dimer in which a variable region is composed of a polypeptide represented by an amino acid sequence consisting of the 1st to 107th amino acids of SEQ ID NO: 41, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence.   
     
     
         6 . A method of eradicating cancer cells or suppressing or inhibiting a proliferation of the cancer cells according to  claim 5 , wherein
 the human antibody κ-type light chain of (1) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 2, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (2) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 8, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (3) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 10, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (4) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 14, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (5) above is a human antibody κ-type light chain in the form of a monomer composed of a polypeptide represented by an amino acid sequence in which cysteine at position 219 has been deleted or substituted by an amino acid other than cysteine in the amino acid sequence of SEQ ID NO: 20, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (6) above is a human antibody κ-type light chain in the form of a monomer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 38, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence;   the human antibody κ-type light chain of (7) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by the amino acid sequence of SEQ ID NO: 40, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence; or   the human antibody κ-type light chain of (8) above is a human antibody κ-type light chain in the form of a dimer composed of a polypeptide represented by an amino acid sequence of SEQ ID NO: 41, an amino acid sequence in which one or a plurality of the amino acids in the amino acid sequence have been substituted, added or deleted, or an amino acid sequence having homology of 95% or more with the amino acid sequence.   
     
     
         7 . A method of eradicating cancer cells or suppressing or inhibiting a proliferation of the cancer cells according to  claim 5 , wherein the object requiring the administration develops lung cancer. 
     
     
         8 . A method of eradicating cancer cells or suppressing or inhibiting a proliferation of the cancer cells according to  claim 5 , wherein the anticancer composition demonstrates a cytotoxicity against cancer cells which are present on a cell surface. 
     
     
         9 . A method of eradicating cancer cells or suppressing or inhibiting a proliferation of the cancer cells according to  claim 5 , comprising: administrating the anticancer composition in a form which enables the anticancer composition to be delivered to pneumocytes from a nose or bronchi.