Activated ADAM10 targeting antibody 1H5 suppresses NOTCH-driven glioma progenitors

A fully-human anti-activated ADAM10 antibody, 1H5, suppresses NOTCH-driven glioma progenitor growth in high-grade glioma models, linked to activated-ADAM10 levels.

• Why it matters: Stem-like glioma progenitor cells in high-grade gliomas rely on NOTCH signaling for self-renewal and survival, and systemic NOTCH inhibition has failed due to toxicity.
• What they did: The study tested 1H5 in patient-derived HGG cell lines and tissues, correlating sensitivity with activated-ADAM10 surface levels, and using ADAM10 shRNA, NOTCH readouts, neurosphere assays, and necroptosis markers.
• The result: 1H5 inhibits NOTCH pathway components and target genes, reduces GPC markers and Sox2- and Ki67-positive cells, and induces necroptosis via survivin loss and increased phosphorylated MLKL, including reduced growth in 3D explants and orthotopic xenografts.

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