uPAR as a novel immunotherapeutic target in recurrent glioblastoma

Glioblastoma (GBM) comprises nearly 15% of primary CNS tumors, and 50% of malignant primary CNS tumors worldwide. Considerable tumoral heterogeneity exists within GBM, leading to inefficacy of current treatments, and the absence of meaningful improvements in frontline therapies in the last 20 years. Through multi-omic analysis of patient-derived primary and recurrent GBM cell lines we identify the urokinase plasminogen activator receptor (uPAR) as a pro-tumorigenic marker of putative brain tumor initiating cells and potential therapeutic target. We find that genetic disruption of uPAR expression impairs pro-tumorigenic characteristics in vitro and in vivo, and uPAR Chimeric Antigen Receptor (CAR) T cells demonstrate potent activity against recurrent GBM patient-derived xenograft models, significantly increasing survival. Notably, uPAR is expressed on GBM-associated macrophages, extending the potential of uPAR CAR Ts to target both GBM and its cognate tumor microenvironment (TME). Togeth..., , , # Data from: uPAR as a novel immunotherapeutic target in recurrent glioblastoma Dataset DOI: [10.5061/dryad.866t1g25g](https://doi.org/10.5061/dryad.866t1g25g) ## Description of the data and file structure **Hydrogen-exchange mass spectrometry** A hydrogen-deuterium exchange mass spectrometry (HDX-MS) dataset, characterizing the binding of nanobodies to deglycosylated uPAR, is described. Briefly, deglycosylated uPAR was prepared by overnight incubation at 37°C with an enzyme cocktail (PNGaseF, neuraminidase, ß-galactosidase and N-acetylglucosaminidase). VHH:uPAR complexes were prepared at a 1:1 molar ratio in PBS, pH 7.4. Using an HDx3-PAL autosampler (Trajan Scientific and Medical), samples were labeled for 3 min by 5-fold dilution in labelling solution (90% D2O in PBS, pH 7.4) for a final deuterium composition of 72%, quenched for 2 min at 4°C by 5-fold dilution in 2 M urea containing 200 mM TCEP and 0.1% formic acid, then 75 µL (23 pmol) was injected onto an immobilized pepsin co...,