Open AccessNovel anticarcinoembryonic antigen antibody–drug conjugate has antitumor activity in the existence of soluble antigen
Author(s) -
Shinmi Daisuke,
Nakano Ryosuke,
Mitamura Keisuke,
SuzukiImaizumi Minami,
Iwano Junko,
Isoda Yuya,
Enokizono Junichi,
Shiraishi Yasuhisa,
Arakawa Emi,
Tomizuka Kazuma,
Masuda Kazuhiro
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1003
Subject(s) - carcinoembryonic antigen , antibody , antigen , conjugate , antibody drug conjugate , cancer , medicine , cancer research , chemistry , immunology , monoclonal antibody , mathematical analysis , mathematics
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.