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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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TEM-GBM trial - scRNAseq and TCR

ABSTRACT: Glioblastoma (GBM) is an immunologically cold brain tumor with poor outcome. We report an interim analysis of a first-in-human dose escalation study investigating Temferon, an advanced therapy medicinal product composed of autologous hematopoietic stem/progenitor cells engineered to express alpha-2 interferon selectively in the myeloid progeny recruited into the GBM tumor microenvironment (TME). Twenty-four newly diagnosed GBM patients were treated following conformal focal radiotherapy and non myeloablative conditioning chemotherapy. The primary objective was to assess safety and tolerability over the first 90 days, secondary objectives were long-term safety, definition of dose and conditioning regimen, and signs of activity. Temferon met the primary outcome of safety, with a toxicity profile consistent with autologous stem cell transplantation. No dose limiting toxicities were recorded up to 4x10^6 Temferon cells/kg, and conditioning with busulfan was selected for further development. Median overall- and progression-free survival from infusion (diagnosis) was 13.2 (16.7) and 6.2 (8.1) months, respectively. Most patients maintained good performance status and quality of life. Genetically engineered cells were detected long-term in the bone marrow and the blood, where minimal amounts of IFN-a were measured. Exploratory analyses on post-treatment brain tissue samples showed the presence of transgenic progeny and immune reprogramming of the TME towards enrichment for inflammatory macrophages and CD8 effector T-cells (EudraCT 2018-001404-11).

INSTRUMENT(S): Not applicable, Chromium Controller with Chromium Next GEM Single Cell 5’ and V(D)J (kits v1.1), Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Matteo Barcella

PROVIDER: E-MTAB-16504 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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