posted on 2023-08-04, 10:20authored byLucie Van Emmenis, Sheng-Yu Ku, Kaitlyn Gayvert, Jonathan R. Branch, Nicholas J. Brady, Subhasree Basu, Michael Russell, Joanna Cyrta, Aram Vosoughi, Verena Sailer, Hussein Alnajar, Etienne Dardenne, Elena Koumis, Loredana Puca, Brian D. Robinson, Michael D. Feldkamp, Annmarie Winkis, Nathan Majewski, Brent Rupnow, Marco M. Gottardis, Olivier Elemento, Mark A. Rubin, Himisha Beltran, David S. Rickman
CELSR3 is a target for T-cell redirection therapeutics. A, CELSR3xCD3 bs-mAb directs T-cell mediated cytotoxicity in CELSR3(+) TCCSUP NLR and PM154 NLR but not CELSR3(−) DU145 NLR, TCCSUP CELSR3 KO cell lines. 5:1 (exp. 1) or 10:1 (exp. 2) pan T cells to tumor cells were added to each well along with CELSR3xCD3 bs-mAb and imaged using the IncuCyte S3 platform. Maximum cell lysis occurred by day 7 timepoint. At least three biological replicates were analyzed from one independent experiment. B, Cell surface expression of CELSR3 on tumor cell lines determined by quantitative flow cytometry and calculated from at least 10,000 events per sample. Dotted line denotes assay lower limit of detection.
The development of effective treatment for patients with NEPC remains an unmet clinical need. We have identified specific surface proteins, including CELSR3, that may serve as novel biomarkers or therapeutic targets for NEPC.