Broad-Spectrum Efficacy of CEACAM6-Targeted Antibody-Drug Conjugate with BET Protein Degrader in Colorectal, Lung, and Breast Cancer Mouse Models.

ABSTRACT: Despite remarkable advances in cancer treatment, most solid cancers remain difficult to cure. We recently developed an antibody-drug conjugate (ADC; 84-EBET) for pancreatic cancer by using the carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) antibody #84.7 and the bromodomain and extra-terminal (BET) protein degrader EBET. In this study, we showed the overexpression of CEACAM6 in colorectal, lung, and breast cancers and the broad-spectrum efficacy of 84-EBET in mouse models of these cancers. In vitro assays using cancer organoids and cell lines of colorectal, lung, and breast cancers revealed that 84-EBET was more potent than ADCs with known approved payloads-DXd, SN38, and monomethyl auristatin E-or standard chemotherapies. In mouse studies, a single injection of 84-EBE

SUBMITTER: Kogai H 

PROVIDER: S-EPMC11876960 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature