Details

Autor(en) / Beteiligte

• Shinmi, Daisuke
• Nakano, Ryosuke
• Mitamura, Keisuke
• Suzuki‐Imaizumi, Minami
• Iwano, Junko
• Isoda, Yuya
• Enokizono, Junichi
• Shiraishi, Yasuhisa
• Arakawa, Emi
• Tomizuka, Kazuma
• Masuda, Kazuhiro

Titel

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

Ist Teil von

• Cancer medicine (Malden, MA), 2017-04, Vol.6 (4), p.798-808

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2017

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. In this study, we succeeded in creating 15‐1‐32, a fully human antibody that recognizes membrane‐bound carcinoembryonic antigen (CEA). 15‐1‐32 shows a higher binding affinity for membrane‐bound CEA than other CEA antibodies, and is only slightly influenced by soluble‐form CEA. 15‐1‐32‐drug conjugate (15‐1‐32‐vcMMAE) showed enhanced antitumor activity against gastric cancer cell lines in the presence of high concentrations of soluble CEA.