The Antibody-Drug Conjugate Sacituzumab Govitecan (IMMU-132) Represents a Potential Novel Therapeutic Strategy in Cholangiocarcinoma.

Cholangiocarcinoma is a rare and aggressive cancer type with limited therapeutic options. Several novel antibody-drug conjugates (ADC) have demonstrated promising antitumor activity in solid tumors. This study aimed to investigate the expression and the potential prognostic role of the protein targets of the recently developed ADCs in cholangiocarcinoma. Moreover, the study aimed to establish patient-derived tumor organoids (PDO) and to employ them for in vitro ADC testing. We evaluated the expression of TROP2, NECTIN4, folate receptor 1, HER2, and HER3 via IHC in a cholangiocarcinoma tissue microarray (n = 113) and analyzed the expression level with respect to clinicopathologic parameters. Furthermore, we generated cholangiocarcinoma PDO culture lines and used them to test the antitumor activity of ADCs in vitro. IHC analyses revealed that TROP2 was the most frequently expressed (91% of cases), followed by folate receptor 1 (51%), NECTIN4 (49%), HER3 (20%), and HER2 (7%). TROP2 showed moderate to high expression (H-score ≥100) in 74% of cases. No significant correlations with overall or disease-free survival, tumor grade, or tumor stage were observed. Six cholangiocarcinoma PDO lines were successfully established (55% success rate). All PDO lines expressed TROP2 concordantly with their parental tumors and showed growth inhibition (IC50 = 0.1-0.4 μg/mL) in response to sacituzumab govitecan (TROP2-targeting ADC). This study reveals that TROP2 is widely expressed in cholangiocarcinoma. Moreover, it provides preclinical evidence for the potential of the use of sacituzumab govitecan as a novel therapeutic strategy in treating patients with cholangiocarcinoma.