Novel Amanitin-Based Antibody-Drug Conjugates Targeting TROP2 for the Treatment of Pancreatic Cancer.

ABSTRACT: Trophoblast cell surface antigen 2 (TROP2) exhibits aberrant expression in pancreatic cancer, correlating with metastasis, advanced tumor stage, and poor prognosis in patients with pancreatic ductal adenocarcinoma. TROP2 has been recognized as a promising therapeutic target for antibody-drug conjugates (ADC), as evidenced by the approval of the anti-TROP2 ADC Trodelvy for the treatment of triple-negative breast cancer (TNBC). In this study, we report the generation of novel second-generation amanitin-based ADCs (ATAC) targeting TROP2, comprising the humanized RS7 antibody of Trodelvy (hRS7) and the highly potent payload amanitin. The specific in vitro binding, efficient antigen internalization, and high cytotoxicity of hRS7 ATACs with EC50 values in the picomolar range in TROP2-expressing

SUBMITTER: Papacharisi E 

PROVIDER: S-EPMC11962393 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature