Diagnosis and treatment of cancer using anti-TMPRSS11E antibody
[Problem to be Solved] An object of the present invention is to provide novel means for the treatment and diagnosis of cancer. [Solution] The present inventors have obtained a monoclonal antibody against TMPRSS11E and found that this antibody binds to a native form of TMPRSS11E, and TMPRSS11E is highly expressed on the cell membranes of cancer cell lines in flow cytometry. This antibody exhibits antibody-dependent cell-mediated cytotoxicity activity (ADCC activity) and antitumor effect based on internalization activity and is promising as a therapeutic target. Moreover, this antibody has neutralization activity against protease activity and is also expected to have effect brought about by the inhibition of TMPRSS11E functions.
1. An antibody binding to a TMPRSS11E protein, the antibody being selected from the following:
(1) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 3, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 4, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 5 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 12, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 13 and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 14;
(2) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 6, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 7, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 8 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 15, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 16 and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 17;
(3) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 9, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 10, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 11 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 18, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 19 and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 20; and
(4) an antibody binding to the same epitope as that via which any antibody of (1) to (3) binds to the TMPRSS11E protein.
2. The antibody according to claim 1 , wherein the antibody has cytotoxic activity.
3. The antibody according to claim 2 , wherein the cytotoxic activity is antibody-dependent cellular cytotoxicity (ADCC activity) and/or complement-dependent cytotoxicity (CDC activity).
4. The antibody according to claim 2 , wherein the antibody has internalization activity.
5. The antibody according to claim 4 , wherein the antibody is conjugated to a cytotoxic substance.
6. The antibody according to any one of claims 2 , 3 , 4 and 5 , wherein the antibody has neutralization activity.
7. A pharmaceutical composition comprising the antibody according to any one of claims 2 , 3 , 4 , 5 and 1 as an active ingredient.
8. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is an anticancer agent.
9. The pharmaceutical composition according to claim 8 , wherein the anticancer agent targets lung cancer, uterine cervix cancer, or esophagus cancer.
10. A diagnostic drug for cancer comprising the antibody according to any of claims 2 , 3 , 4 , 6 and 1 .
11. A pharmaceutical composition comprising the antibody according to claim 6 as an active ingredient.
12. The pharmaceutical composition according to claim 11 , wherein the pharmaceutical composition is an anticancer agent.
13. The pharmaceutical composition according to claim 12 , wherein the anticancer agent targets lung cancer, uterine cervix cancer, or esophagus cancer.
14. A diagnostic drug for cancer comprising the antibody according to claim 6 .