Diagnosis and treatment of cancer using anti-TM4SF20 antibody
The present invention relates to an antibody binding to a TM4SF20 protein and the diagnosis and treatment of cancer using the antibody. Specifically, the present invention provides an anti-TM4SF20 antibody and a pharmaceutical composition (e.g., an anticancer agent and a diagnostic drug for cancer) comprising the antibody as an active ingredient.
1. An isolated monoclonal antibody binding to a TM4SF20 protein, wherein the antibody binds to amino acids 168-184 in the amino acid sequence of SEQ ID NO: 116.
2. The antibody according to claim 1 , wherein the antibody has cytotoxic activity, wherein the cytotoxic activity is antibody-dependent cellular cytotoxicity (ADCC activity) or complement-dependent cytotoxicity (CDC activity).
3. The antibody according to claim 1 , 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: 79, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 80, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 81 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 82, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 83, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 84;
(2) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 85, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 86, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 87 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 88, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 89, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 90;
(3) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 91, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 92, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 93 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 94, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 95, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 96;
(4) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 97, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 98, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 99 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 100, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 101, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 102;
(5) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 103, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 104, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 105 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 106, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 107, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 108;
(6) an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence represented by SEQ ID NO: 109, heavy chain CDR2 having the amino acid sequence represented by SEQ ID NO: 110, and heavy chain CDR3 having the amino acid sequence represented by SEQ ID NO: 111 and comprising a light chain variable region comprising light chain CDR1 having the amino acid sequence represented by SEQ ID NO: 112, light chain CDR2 having the amino acid sequence represented by SEQ ID NO: 113, and light chain CDR3 having the amino acid sequence represented by SEQ ID NO: 114;
(7) an antibody of (1) to (6), wherein the antibody is a humanized antibody, and has ADCC or CDC activity equivalent to that of the any antibody of (1) to (6); and
(8) an antibody binding to the same epitope as that via which any antibody of (1) to (6) binds to the TM4SF20 protein.
4. A pharmaceutical composition comprising an antibody according to claim 1 as an active ingredient.
5. A method for diagnosing cancer, comprising the following steps:
(a) preparing a sample isolated from a test subject; and
(b) detecting the expression level of a TM4SF20 protein in the sample with the isolated monoclonal antibody of claim 1 ; (c) diagnosing a cancer based on the expression level of the TM4SF20 protein.
6. The diagnosis method according to claim 5 , wherein the diagnosis method is intended for the diagnosis of cancer selected from stomach cancer, lung adenocarcinoma, pancreatic cancer, and colon cancer.
7. A diagnostic drug for cancer comprising an antibody according to claim 1 .
8. The diagnostic drug according to claim 7 , wherein the diagnostic drug is intended for the diagnosis of cancer selected from stomach cancer, lung adenocarcinoma, pancreatic cancer, and colon cancer.