Anti-CLDN6 antibody
The present invention relates to an antibody binding to Claudin6 (CLDN6) expressed on a cell membrane. The antibody of the present invention recognizes human CLDN6 present in a native form on cell membrane surface and exhibits cytotoxicity through ADCC and/or CDC activities against cancer cell lines highly expressing human CLDN6. Moreover, the antibody of the present invention has cell growth inhibitory effect through conjugation with toxin on cancer cell lines highly expressing human CLDN6. The human CLDN6 is overexpressed in tumor tissues (lung adenocarcinoma, gastric cancer, and ovarian cancer), although its expression is not observed in normal tissues. Thus, the anti-CLDN6 antibody is expected to highly accumulate in tumors highly expressing human CLDN6 and can serve as a very effective antitumor agent.
1. An isolated monoclonal antibody selected from the group consisting of (a) and (b):
(a) an antibody comprising a heavy chain variable region having CDR1 having the amino acid sequence represented by SEQ ID NO: 40, CDR2 having the amino acid sequence represented by SEQ ID NO: 41, and CDR3 having the amino acid sequence represented by SEQ ID NO: 42 and comprising a light chain variable region having CDR1 having the amino acid sequence represented by SEQ ID NO: 43, CDR2 having the amino acid sequence represented by SEQ ID NO: 44, and CDR3 having the amino acid sequence represented by SEQ ID NO: 45; and
(b) an antibody which blocks the binding of the antibody of (a) to CLDN6,
wherein said antibody selected from the group consisting of (a) and (b) has cytotoxicity, and has 50% or less avidity for CLDN9 as set forth in SEQ ID NO: 48 compared with its avidity for CLDN6.
2. The isolated monoclonal antibody according to claim 1 , which has ADCC activity.
3. The isolated monoclonal antibody according to claim 1 , which has CDC activity.
4. The isolated monoclonal antibody according to claim 1 , which is conjugated with a cytotoxic substance.
5. The isolated monoclonal antibody according to claim 1 , which has 30% or less avidity for CLDN9 as set forth in SEQ ID NO:48 compared with its avidity for CLDN6.
6. The isolated monoclonal antibody according to claim 1 , which has 10% or less avidity for CLDN9 as set forth in SEQ ID NO:48 compared with its avidity for CLDN6.
7. A pharmaceutical composition for treating cancer, comprising the isolated monoclonal antibody of claim 1 .
8. The pharmaceutical composition according to claim 7 , wherein the cancer is a cancer highly expressing CLDN6.
9. The pharmaceutical composition according to claim 7 , wherein the cancer is lung adenocarcinoma, gastric cancer, or ovarian cancer.