title: 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. 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.
authors.affiliation: Research Core Function Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shinmi
authors.affiliation: Research Core Function Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nakano
authors.affiliation: Oncology Research Laboratories, Oncology R&D Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mitamura
authors.affiliation: Translational Research Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Suzuki-Imaizumi
authors.affiliation: Research Core Function Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Iwano
authors.affiliation: Innovative Technology Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Isoda
authors.affiliation: Research Core Function Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Enokizono
authors.affiliation: R&D Planning Department, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Fuji Research Park, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Arakawa
authors.affiliation: Innovative Technology Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Tomizuka
authors.affiliation: Innovative Technology Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry*; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D009842:Oligopeptides; C495575:monomethyl auristatin E
keywords: Antibody; CEA; antibody-drug conjugate; esophageal cancer; gastric cancer