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Targeted delivery of tumor necrosis factor in combination with lomustine induces a T-cell dependent regression of glioblastoma

ABSTRACT: Glioblastoma is the most aggressive primary brain tumor with an unmet need for more effective therapies. Here we report that the combination of L19TNF, an antibody-cytokine fusion protein based on tumor necrosis factor that selectively localizes on the tumor neo-vasculature, with the alkylating agent lomustine, can induce tumor regression in orthotopic glioma-bearing mice and patients with recurrent glioblastoma. Mechanistically, this striking synergy crucially depended on T cells and involved activation of the tumor endothelium, tumor DNA damage, treatment-associated tumor necrosis, increased antigen presentation on MHC class I and tumor immune cell infiltration, as well as decreased tumor-associated immunosuppression. The clinical translation of this approach is ongoing, but already shows durable responses in the first recurrent glioblastoma patient cohort treated with L19TNF in combination with lomustine (NCT04573192).

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Permanent Cell Line Cell, Epithelial Cell

DISEASE(S): Brain Cancer

SUBMITTER: Marcel Bühler

LAB HEAD: Tobias Weiss

PROVIDER: PXD041234 | Pride | 2026-02-23

REPOSITORIES: Pride

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			Action	DRS
	20210830_002_TumorCells_Pool_QC_1_S312814.d.zip	Other
	20210830_003_ICK_TumorCells_CCNUL19_5_S312797.d.zip	Other
	20210830_004_EndoCells_LibraryPool_3_S312809.d.zip	Other
	20210830_005_ICK_TumorCells_L19_5_S312780.d.zip	Other
	20210830_006_ICK_EndoCells_CCNU_1_S312798.d.zip	Other

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