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Title:
Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma | Cancer Immunology, Immunotherapy
Description:
Background The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting. Methods We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9–18 vaccines containing 107 cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the ClinicalTrials.gov identifier NCT00846456. Results Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test). Conclusion These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.
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Keywords {🔍}
cells, patients, cancer, article, stem, tumor, google, scholar, cell, pubmed, cas, glioblastoma, response, vaccination, autologous, dcs, immune, dendritic, oslo, study, brain, days, human, treated, antigens, fig, data, patient, cscs, survival, mrna, gscs, norway, clinical, targeting, vitro, cultures, gsc, immunotherapy, vaccine, tumors, group, research, vikmo, standard, rna, compared, control, htert, performed,
Topics {✒️}
einar osland vik-mo granulocyte–macrophage-colony-stimulating factor antigen-specific t-cell response stein sæbøe-larssen article vik-mo vik-mo eo preclinical full-scale evaluation tumor necrosis factor-α dcs t-cell inductions post-operative mri volumes article download pdf monocyte-derived autologous dcs post-operative tumor volume efficient tumour formation post-vaccine peripheral blood conventional radio-chemotherapy anne-marie rasmussen & gustav gaudernack mrna-transfected dendritic cells small contrast-enhancing lesion superase•ln rnase inhibitor post-operative radio-chemotherapy effective antigen-presenting cells contrast-enhancing lesions decreased mountain view transcriptional profiles allogeneic cell lines prolong progression-free survival cancer stem cell short-lived rna constructs csc–progenitor cell population sphere-forming cells derived dendritic cell vaccination glioblastoma-derived tumorspheres identify prolong recurrence-free survival telomerase-derived peptide vaccination autologous tumorsphere cultures autologous gsc-amplified mrna dendritic cells loaded gcp-qualified external monitor vik-mo increase progression-free survival human dendritic cells induced t-lymphocyte proliferation t-cell activation csc gene signature dendritic cells transfected post-operative radiotherapy receive dc immunotherapy gsc-specific immune response stem cell population
Questions {❓}
- Johnson RS, Walker AI, Ward SJ (2009) Cancer vaccines: will we ever learn?
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headline:Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma
description:The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting. We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9–18 vaccines containing 107 cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the
ClinicalTrials.gov
identifier NCT00846456. Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test). These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.
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Brain cancer stem cell
Tumorsphere
Glioblastoma
Dendritic cell
Immunotherapy
Autologous cell culture
Oncology
Immunology
Cancer Research
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headline:Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma
description:The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting. We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9–18 vaccines containing 107 cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the
ClinicalTrials.gov
identifier NCT00846456. Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test). These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.
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Brain cancer stem cell
Tumorsphere
Glioblastoma
Dendritic cell
Immunotherapy
Autologous cell culture
Oncology
Immunology
Cancer Research
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address:
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address:
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address:
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name:Stein Sæbøe-Larssen
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address:
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address:
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name:Anne-Marie Rasmussen
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address:
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address:
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address:
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type:PostalAddress
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address:
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address:
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type:PostalAddress
type:Organization
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address:
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type:PostalAddress
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address:
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type:PostalAddress
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PostalAddress:
name:Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway
name:Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Clinical Cancer Research, Oslo University Hospital, Oslo, Norway
name:Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Ophthalmology, Center for Eye Research, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Radiology, Oslo University Hospital, Oslo, Norway
name:Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Cellular Therapy, Cancer Clinic, Oslo University Hospital, Oslo, Norway
name:Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Ex Vivo Cell Laboratory, Institute of Immunology, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
name:Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
name:Department of Oncology, Cancer Clinic, Oslo University Hospital, Oslo, Norway
name:Department of Clinical Cancer Research, Oslo University Hospital, Oslo, Norway
name:Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
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name:Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway
name:Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
name:Cancer Stem Cell Innovation Center, Oslo University Hospital, Oslo, Norway
name:Norwegian Stem Cell Center, Oslo University Hospital, Oslo, Norway
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