Development of a bispecific antibody-drug conjugate targeting EpCAM and CLDN3 for the treatment of multiple solid tumors.

ABSTRACT: Epithelial cell adhesion molecule (EpCAM), a tumor antigen for antibody-drug conjugates (ADCs), is highly expressed in many epithelial cancers. However, the clinical progress of EpCAM ADCs has been challenging, primarily due to their toxicity in normal high-expression tissues such as the gastrointestinal tract. CLDN3 is highly co-expressed with EpCAM in various human malignancies, coupled with its minimal presence in normal tissues, rendering it an ideal target for developing potent therapeutic ADCs. Here, we developed a bispecific ADC (BsADC) targeting EpCAM and CLDN3, designed to avoid toxicity in normal tissues with high EpCAM expression. The parental monoclonal antibodies (mAbs) were screened for high binding and endocytosis activities on tumor cell lines. We then modified them into mo

SUBMITTER: Luo M 

PROVIDER: S-EPMC11889805 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature