bioRxiv (Cold Spring Harbor Laboratory)
CRISPR-Induced NUT Suppression Promotes Differentiation and Enhances Trop2-Targeted Immunocytokine Response in NUT Carcinoma
October 2025 • Juyoung Choi, Daesik Kim, Joo Youn Oh, Hee Geon Park, Hwa Lin Yi, Yurimi Lee, Hoyeon Jeong, Jiyoung Song, Minjung Sung, Eun Sol Chang, Kyungsoo Jung,…
Abstract NUT carcinoma (NC) is an aggressive malignancy driven by NUTM1 gene rearrangements with limited therapeutic options. Here, we show that direct suppression of NUTM1 using CRISPR/Cas9 induces squamous-like differentiation and upregulates TROP2 expression in NC cells. Building on this finding, we developed a TROP2–interferon beta (IFN-β) mutein immunocytokine that selectively targets TROP2-expressing tumors. Combined NUTM1 suppression and TROP2-targeted immunotherapy synergistically enhanced cytotoxic and im…