Data from: 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).
Together, these data illustrate the potency and therapeutic potential of
targeting uPAR in GBM.