OS08.7.A Lomustine and the immunocytokine L19TNF are a promising treatment combination for recurrent glioblastoma

Abstract Background Treatment options for recurrent glioblastoma are limited and with the possible exception of regorafenib, no agent has demonstrated superior activity to lomustine. Therefore, there is an urgent need more effective treatment strategies glioblastoma. Here, we investigated different combinations based on tumor-stroma targeting antibody-cytokine fusion protein L19TNF in preclinical glioma models translated most combination patients Material Methods Orthotopic immunocompetent mouse were used study anti-glioma anti-PD1, bevacizumab or Tumor growth was monitored by MRI. Flow cytometry microscopy characterize tumor-infiltrating-immune cells. MHC immunoaffinity purification mass spectrometry immunopeptidome. Genetic immune-dependent effects. Subsequently, efficient within a phase I/II clinical trial (NCT04573192). Results The lomustine strong synergistic anti-tumor two orthotopic cured majority tumor-bearing mice. In contrast, anti-PD-1 had only activity. Furthermore, compared monotherapies, led strongest increase tumor-infiltrating lymphoid cells as flow microsopy highest number peptides presented context MHC-I. effect abrograted genetic immunodeficient models. well tolerated first treated observed partial tumor responses also unmethylated MGMT promoter. Conclusion promising currently recruited