Anti-podoplanin antibody
The present invention provides a cancer cell-specific anti-podoplanin antibody or an antigen-binding fragment thereof having an epitope in a Thr85-containing region of an amino acid sequence of human podoplanin represented by SEQ ID NO: 1, the Thr85 having a sialylated O-glycan added thereto.
1. A cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof, comprising the following six CDR amino acid sequences:
heavy chain CDR1:
(SEQ ID NO: 2)
GFTFSNAAMY
heavy chain CDR2:
(SEQ ID NO: 3)
RIRSKPNNYATYYTDSVKG
heavy chain CDR3:
(SEQ ID NO: 4)
TVGGNNYAAAY
light chain CDR1:
(SEQ ID NO: 5)
RSSQSLVHSNGNTYLE
light chain CDR2:
(SEQ ID NO: 6)
KVSNRFS
light chain CDR3:
(SEQ ID NO: 7)
FQVTHDPFT.
2. The cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof according to claim 1 , having one or more N-glycans bound to an Fc region thereof and having no fucose bound to N-acetylglucosamine at a reducing end of the N-glycan(s).
3. A nucleic acid encoding the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof according to claim 1 .
4. An expression vector, comprising the nucleic acid as claimed in claim 3 .
5. A transformant, comprising the expression vector as claimed in claim 4 .
6. A pharmaceutical composition, comprising, as an effective ingredient thereof, the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof as claimed in claim 1 .
7. A pharmaceutical composition, comprising, as an effective ingredient thereof, the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof as claimed in claim 1 to which a substance having an anti-cancer activity has been bound.
8. A method of treating cancer, wherein said cancer expresses podoplanin, in a subject, which comprises administering to the subject the pharmaceutical composition according to claim 6 .
9. A method of treating cancer, wherein said cancer expresses podoplanin, in a subject, which comprises administering to the subject the pharmaceutical composition according to claim 7 .
10. A cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof, comprising the following six CDR amino acid sequences:
heavy chain CDR1:
(SEQ ID NO: 2)
GFTFSNAAMY,
heavy chain CDR2:
(SEQ ID NO: 3)
RIRSKPNNYATYYTDSVKG,
heavy chain CDR3:
(SEQ ID NO: 4)
TVGGNNYAAAY,
light chain CDR1:
(SEQ ID NO: 5)
RSSQSLVHSNGNTYLE,
light chain CDR2:
(SEQ ID NO: 6)
KVSNRFS,
and
light chain CDR3:
(SEQ ID NO: 7)
FQVTHDPFT;
wherein the heavy chain has an amino acid sequence that:
is represented by SEQ ID NO: 8 or 10;
is obtained by addition, substitution, or deletion of one to several amino acids from the amino acid sequence represented by SEQ ID NO: 8 or 10;
has 80% or more identity to the amino acid sequence represented by SEQ ID NO: 8 or 10; and
wherein the light chain has an amino acid sequence that:
is represented by SEQ ID NO: 9 or 11;
is obtained by addition, substitution or deletion of one to several amino acids from the amino acid sequence represented by SEQ ID NO: 9 or 11, or
has 80% or more identity to the amino acid sequence represented by SEQ ID NO: 9 or 11.
11. The cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof according to claim 10 , having one or more N-glycans bound to an Fc region thereof and having no fucose bound to N-acetylglucosamine at a reducing end of the N-glycan(s).
12. A nucleic acid encoding the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof according to claim 10 .
13. An expression vector, comprising the nucleic acid as claimed in claim 11 .
14. A transformant, comprising the expression vector as claimed in claim 13 .
15. A pharmaceutical composition, comprising, as an effective ingredient thereof, the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof as claimed in claim 10 .
16. A pharmaceutical composition, comprising, as an effective ingredient thereof, the cancer cell-specific anti-podoplanin antibody or antigen-binding fragment thereof as claimed in claim 10 to which a substance having an anti-cancer activity has been bound.
17. A method of treating cancer, wherein said cancer expresses podoplanin, in a subject, which comprises administering to the subject the pharmaceutical composition according to claim 15 .
18. A method of treating cancer, wherein said cancer expresses podoplanin, in a subject, which comprises administering to the subject the pharmaceutical composition according to claim 16 .