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

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.