Pharmaceutical composition for treatment and/or prevention of cancer
It is intended to provide a CAPRIN-1-targeting antibody superior in antitumor activity to conventional antibodies, and use thereof as a therapeutic and/or preventive agent for a cancer. The present invention provides an antibody targeting a CAPRIN-1 polypeptide specifically expressed on the surface of cancer cells, and use of the antibody as a therapeutic and/or preventive agent for a cancer. The present invention provides an antibody which comprises a heavy chain variable region comprising complementarity-determining regions of SEQ ID NOs: 1, 2, and 3 and a light chain variable region comprising complementarity-determining regions of SEQ ID NOs: 4, 5, and 6 and has immunological reactivity with a CAPRIN-1 protein, or a fragment thereof, and a pharmaceutical composition for the treatment and/or prevention of a cancer, comprising this antibody or fragment as an active ingredient.
1. An antibody or an antigen-binding fragment thereof, which comprises
a heavy chain variable region comprising complementarity-determining regions of SEQ ID NOs: 1, 2, and 3 and
a light chain variable region comprising complementarity-determining regions of SEQ ID NOs: 4, 5, and 6, and
has immunological reactivity with a CAPRIN-1 protein.
2. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 15.
3. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 10, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 15.
4. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 15.
5. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 13.
6. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 12.
7. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 12.
8. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 13.
9. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 10, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 14.
10. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 8, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 11.
11. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 11.
12. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 9, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 15.
13. The antibody or the fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 20, and
the light chain variable region comprises the amino acid sequence of SEQ ID NO: 21.
14. The antibody or the fragment thereof according to claim 1 , wherein the antibody is a human antibody, a humanized antibody, a chimeric antibody, a single-chain antibody, or a multispecific antibody.
15. The antibody or the fragment thereof according to claim 1 , wherein the antibody or the fragment is conjugated with an antitumor agent.
16. The antibody according to claim 1 , wherein the antibody has a heavy chain constant region and comprises the substitution of one or more amino acids in the heavy chain constant region.
17. The antibody according to claim 1 , wherein the antibody is an antibody lacking fucose added to N-acetylglucosamine at the sugar chain reducing end of a N-glycoside-linked sugar chain attached to the heavy chain constant region.
18. An antibody composition comprising:
an antibody wherein the antibody is an antibody lacking fucose added to N-acetylglucosamine at the sugar chain reducing end of a N-glycoside-linked sugar chain attached to the heavy chain constant region, and
an antibody according to claim 1 having fucose added to N-acetylglucosamine at the sugar chain reducing end of a N-glycoside-linked sugar chain attached to the heavy chain constant region.
19. A cell producing an antibody according to claim 17 .
20. A pharmaceutical composition for the treatment of a CAPRIN-1-expressing cancer, comprising an antibody or a fragment thereof according to claim 1 as an active ingredient.
21. The pharmaceutical composition according to claim 20 , wherein the CAPRIN-1-expressing cancer is breast cancer, kidney cancer, pancreatic cancer, colorectal cancer, lung cancer, brain tumor, stomach cancer, uterine cancer, ovary cancer, prostate cancer, bladder cancer, esophagus cancer, leukemia, lymphoma, liver cancer, gallbladder cancer, sarcoma, mastocytoma, melanoma, adrenal cortex cancer, Ewing's tumor, Hodgkin's lymphoma, mesothelioma, multiple myeloma, testicle cancer, thyroid cancer, or head and neck cancer.
22. A combination drug product for the treatment of a CAPRIN-1-expressing cancer, comprising a pharmaceutical composition according to claim 20 and a pharmaceutical composition comprising an antitumor agent.
23. A DNA encoding an antibody or a fragment thereof according to claim 1 .
24. A method for treating a CAPRIN-1-expressing cancer, comprising administering an antibody or a fragment thereof according to claim 1 to a subject.