{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Matteo Barcella"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-16504"],"description":["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)."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - Tumor was dissociated using the ”Tumor Dissociation Kit” (Miltenyi Biotec), lysed to eliminate red blood cells with Ammonium Chloride Solution Lysis Buffer (ACK) (Stem Cell Technologies), purified using “Debris removal kit” (Miltenyi Biotec) and “Dead cell removal kit” (Miltenyi Biotec), and separated into a CD45+ and CD45- fraction by human CD45 (TIL) MicroBeads (Miltenyi Biotec). Both fractions were used, either fresh or frozen, for 10x single-cell RNA sequencing.","Sample Collection - Fresh tumor material was obtained from some Temferon patients or other control patients treated according to standard-of-care when undergoing second surgery for progressive disease. The control patients have agreed to the use of their biological material for research purposes and signed the relevant informed consent forms from the Department of Neurosurgery of the San Raffaele Hospital.","Sequencing - 5′ gene expression library construction and paired-end sequencing was performed on Illumina NovaSeq ollowing manufacturer's protocol.","Library Construction - Single cell RNA and V(D)J libraries were prepared with the Chromium Next GEM Single Cell 5’ and V(D)J Reagents Kits v1.1 (10X Genomics). Briefly, after CD45 selection, at least 900 cells were resuspended at the appropriate concentration for loading into the Chromium Next GEM Single Cell 5’ and V(D)J Reagents Kits v1.1chip according to the manufacturer’s protocol"],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Raw data counts produced with CellRanger 10X genomics (count and vdj commands)"],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Not applicable","Chromium Controller with Chromium Next GEM Single Cell 5’ and V(D)J (kits v1.1)","Illumina NovaSeq 6000"],"study_type":["RNA-seq of coding RNA from single cells"],"species":["Homo sapiens"],"pubmed_authors":["Matteo Barcella"],"additional_accession":[]},"is_claimable":false,"name":"TEM-GBM trial - scRNAseq and TCR","description":"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).","dates":{"release":"2026-03-31T00:00:00Z","modification":"2026-03-31T10:51:28.895Z","creation":"2026-01-02T14:39:49.379Z"},"accession":"E-MTAB-16504","cross_references":{"ENA":["ERP187201"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005684","EFO_0005518","EFO_0003816","EFO_0004184"]}}