2. Academic Validation
  3. Novel anticarcinoembryonic antigen antibody-drug conjugate has antitumor activity in the existence of soluble antigen

Novel anticarcinoembryonic antigen antibody-drug conjugate has antitumor activity in the existence of soluble antigen

  • Cancer Med. 2017 Apr;6(4):798-808. doi: 10.1002/cam4.1003.
Daisuke Shinmi 1,  Ryosuke Nakano 1,  Keisuke Mitamura 2,  Minami Suzuki-Imaizumi 3,  Junko Iwano 1,  Yuya Isoda 4,  Junichi Enokizono 1,  Yasuhisa Shiraishi 5,  Emi Arakawa 6,  Kazuma Tomizuka 4,  Kazuhiro Masuda 4
Affiliations

Affiliations

  • 1 Research Core Function Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
  • 2 Oncology Research Laboratories, Oncology R&D Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
  • 3 Translational Research Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
  • 4 Innovative Technology Laboratories, Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
  • 5 R&D Planning Department, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
  • 6 Fuji Research Park, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
PMID: 28211613 DOI: 10.1002/cam4.1003
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.

Keywords

Antibody; CEA; antibody-drug conjugate; esophageal cancer; gastric cancer.

Figures
Products