Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen
Abstract Carcinoembryonic antigen (CEA) is a classic tumor‐specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti‐CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti‐CEA antibody therapies. Be...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1003 |
| _version_ | 1798001976072470528 |
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| author | Daisuke Shinmi Ryosuke Nakano Keisuke Mitamura Minami Suzuki‐Imaizumi Junko Iwano Yuya Isoda Junichi Enokizono Yasuhisa Shiraishi Emi Arakawa Kazuma Tomizuka Kazuhiro Masuda |
| author_facet | Daisuke Shinmi Ryosuke Nakano Keisuke Mitamura Minami Suzuki‐Imaizumi Junko Iwano Yuya Isoda Junichi Enokizono Yasuhisa Shiraishi Emi Arakawa Kazuma Tomizuka Kazuhiro Masuda |
| author_sort | Daisuke Shinmi |
| collection | DOAJ |
| description | Abstract Carcinoembryonic antigen (CEA) is a classic tumor‐specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti‐CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti‐CEA antibody therapies. Because of this, we have created the novel anti‐CEA antibody, 15‐1‐32, which exhibits stronger binding to membrane‐bound CEA on cancer cells than existing anti‐CEA antibodies. 15‐1‐32 also shows poor affinity for soluble CEA; thus, the binding activity of 15‐1‐32 to membrane‐bound CEA is not influenced by soluble CEA. In addition, we constructed a 15‐1‐32‐monomethyl auristatin E conjugate (15‐1‐32‐vcMMAE) to improve the therapeutic efficacy of 15‐1‐32. 15‐1‐32‐vcMMAE showed enhanced antitumor activity against gastric cancer cell lines. Unlike with existing anti‐CEA antibody therapies, antitumor activity of 15‐1‐32‐vcMMAE was retained in the presence of high concentrations of soluble CEA. |
| first_indexed | 2024-04-11T11:44:45Z |
| format | Article |
| id | doaj.art-bb89aaf8f1514e1dadc670cc4bef52df |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-11T11:44:45Z |
| publishDate | 2017-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-bb89aaf8f1514e1dadc670cc4bef52df2022-12-22T04:25:42ZengWileyCancer Medicine2045-76342017-04-016479880810.1002/cam4.1003Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigenDaisuke Shinmi0Ryosuke Nakano1Keisuke Mitamura2Minami Suzuki‐Imaizumi3Junko Iwano4Yuya Isoda5Junichi Enokizono6Yasuhisa Shiraishi7Emi Arakawa8Kazuma Tomizuka9Kazuhiro Masuda10Research Core Function Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanResearch Core Function Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanOncology Research Laboratories Oncology R&D Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanTranslational Research Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanResearch Core Function Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanInnovative Technology Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanResearch Core Function Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanR&D Planning Department R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanFuji Research Park R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanInnovative Technology Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanInnovative Technology Laboratories Research Functions Unit R&D Division Kyowa Hakko Kirin Co., Ltd. Tokyo JapanAbstract Carcinoembryonic antigen (CEA) is a classic tumor‐specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti‐CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti‐CEA antibody therapies. Because of this, we have created the novel anti‐CEA antibody, 15‐1‐32, which exhibits stronger binding to membrane‐bound CEA on cancer cells than existing anti‐CEA antibodies. 15‐1‐32 also shows poor affinity for soluble CEA; thus, the binding activity of 15‐1‐32 to membrane‐bound CEA is not influenced by soluble CEA. In addition, we constructed a 15‐1‐32‐monomethyl auristatin E conjugate (15‐1‐32‐vcMMAE) to improve the therapeutic efficacy of 15‐1‐32. 15‐1‐32‐vcMMAE showed enhanced antitumor activity against gastric cancer cell lines. Unlike with existing anti‐CEA antibody therapies, antitumor activity of 15‐1‐32‐vcMMAE was retained in the presence of high concentrations of soluble CEA.https://doi.org/10.1002/cam4.1003Antibodyantibody–drug conjugateCEAesophageal cancergastric cancer |
| spellingShingle | Daisuke Shinmi Ryosuke Nakano Keisuke Mitamura Minami Suzuki‐Imaizumi Junko Iwano Yuya Isoda Junichi Enokizono Yasuhisa Shiraishi Emi Arakawa Kazuma Tomizuka Kazuhiro Masuda Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen Cancer Medicine Antibody antibody–drug conjugate CEA esophageal cancer gastric cancer |
| title | Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen |
| title_full | Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen |
| title_fullStr | Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen |
| title_full_unstemmed | Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen |
| title_short | Novel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen |
| title_sort | novel anticarcinoembryonic antigen antibody drug conjugate has antitumor activity in the existence of soluble antigen |
| topic | Antibody antibody–drug conjugate CEA esophageal cancer gastric cancer |
| url | https://doi.org/10.1002/cam4.1003 |
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