Anti-CXADR antibody
An object is to find a target molecule effective for cancer treatments and the like and to provide an antibody capable of specifically binding to the molecule, an anticancer agent comprising the antibody as an active ingredient, and so forth. Hence, prostate cancer cell lines (LNCaP-CR cells and LNCaP cells) were compared by SST-REX, and CXADR was identified as a molecule involved in tumor formation and so on. Then, a monoclonal antibody against CXADR was prepared, and the anti-cancer activity, ADCC activity, CDC activity, and so forth were examined. The result revealed that an antibody capable of binding to an epitope present at positions 181 to 230 of a CXADR protein derived from human exhibited an anti-cancer activity against prostate cancer cells, pancreatic cancer cells, and colorectal cancer cells. Further, it was also revealed that the antibody had an ADCC activity and a CDC activity. Moreover, the structures of light chain and heavy chain variable regions of the antibody were successfully determined.
1. An antibody capable of binding to an epitope present at positions 181 to 230 of human CXADR protein, wherein said antibody is selected from the group consisting of (a) and (b):
(a) an antibody comprising a light chain variable region and a heavy chain variable region, wherein the light chain variable region comprises complementarity determining regions (CDRs) 1 to 3 which comprise the amino acid sequences set forth in SEQ ID NOs: 1 to 3, respectively, and wherein the heavy chain variable region comprises CDRs 1 to 3 which comprise the amino acid sequences set forth in SEQ ID NOs: 6 to 8, respectively; and
(b) an antibody comprising a light chain variable region and a heavy chain variable region, wherein the light chain variable region comprises CDRs 1 to 3 which comprise the amino acid sequences set forth in SEQ ID NOs: 11 to 13, respectively, and wherein the heavy chain variable region comprises CDRs 1 to 3 which comprise the amino acid sequences set forth in SEQ ID NOs: 16 to 18, respectively.
2. A pharmaceutical composition comprising the antibody according to claim 1 as an active ingredient, and a carrier.
3. A method for detecting the presence or absence of a human CXADR protein in a sample isolated from a patient who has cancer or who is suspected of having cancer, the method comprising reacting the sample with the antibody according to claim 1 , and detecting whether the antibody binds to the human CXADR protein.
4. A method for treating CXADR-expressing cancer, comprising administering an effective amount of the antibody according to claim 1 to a patient in need of such treatment.
5. The antibody according to claim 1 , wherein the light chain variable region of said antibody comprises the amino acid sequence set forth in SEQ ID NO: 5 from which a signal sequence is removed; or comprises the amino acid sequence set forth in SEQ ID NO: 5 from which a signal sequence is removed and wherein ten or fewer amino acids in the framework region are substituted, deleted, added, and/or inserted,
and wherein the heavy chain variable region of said antibody comprises the amino acid sequence set forth in SEQ ID NO: 10 from which a signal sequence is removed; or comprises the amino acid sequence set forth in SEQ ID NO: 10 from which a signal sequence is removed and wherein ten or fewer amino acids in the framework region are substituted, deleted, added, and/or inserted.
6. The antibody according to claim 1 , wherein the light chain variable region of said antibody comprises the amino acid sequence set forth in SEQ ID NO: 15 from which a signal sequence is removed; or comprises the amino acid sequence set forth in SEQ ID NO: 15 from which a signal sequence is removed and wherein ten or fewer amino acids in the framework region are substituted, deleted, added, and/or inserted,
and wherein the heavy chain variable region of said antibody comprises the amino acid sequence set forth in SEQ ID NO: 20 from which a signal sequence is removed; or comprises the amino acid sequence set forth in SEQ ID NO: 20 from which a signal sequence is removed and wherein ten or fewer amino acids in the framework region are substituted, deleted, added, and/or inserted.
7. A method for treating CXADR-expressing cancer, comprising administering an effective amount of an antibody capable of binding to an epitope present at positions 181 to 230 of human CXADR protein to a patient in need of such treatment.