Cargando…
Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma
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 o...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755221/ https://www.ncbi.nlm.nih.gov/pubmed/23817721 http://dx.doi.org/10.1007/s00262-013-1453-3 |
_version_ | 1782281963718049792 |
---|---|
author | Vik-Mo, Einar Osland Nyakas, Marta Mikkelsen, Birthe Viftrup Moe, Morten Carstens Due-Tønnesen, Paulina Suso, Else Marit Inderberg Sæbøe-Larssen, Stein Sandberg, Cecilie Brinchmann, Jan E. Helseth, Eirik Rasmussen, Anne-Marie Lote, Knut Aamdal, Steinar Gaudernack, Gustav Kvalheim, Gunnar Langmoen, Iver A. |
author_facet | Vik-Mo, Einar Osland Nyakas, Marta Mikkelsen, Birthe Viftrup Moe, Morten Carstens Due-Tønnesen, Paulina Suso, Else Marit Inderberg Sæbøe-Larssen, Stein Sandberg, Cecilie Brinchmann, Jan E. Helseth, Eirik Rasmussen, Anne-Marie Lote, Knut Aamdal, Steinar Gaudernack, Gustav Kvalheim, Gunnar Langmoen, Iver A. |
author_sort | Vik-Mo, Einar Osland |
collection | PubMed |
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 10(7) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-013-1453-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3755221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-37552212013-09-05 Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma Vik-Mo, Einar Osland Nyakas, Marta Mikkelsen, Birthe Viftrup Moe, Morten Carstens Due-Tønnesen, Paulina Suso, Else Marit Inderberg Sæbøe-Larssen, Stein Sandberg, Cecilie Brinchmann, Jan E. Helseth, Eirik Rasmussen, Anne-Marie Lote, Knut Aamdal, Steinar Gaudernack, Gustav Kvalheim, Gunnar Langmoen, Iver A. Cancer Immunol Immunother Original Article 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 10(7) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-013-1453-3) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2013-07-02 2013 /pmc/articles/PMC3755221/ /pubmed/23817721 http://dx.doi.org/10.1007/s00262-013-1453-3 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article Vik-Mo, Einar Osland Nyakas, Marta Mikkelsen, Birthe Viftrup Moe, Morten Carstens Due-Tønnesen, Paulina Suso, Else Marit Inderberg Sæbøe-Larssen, Stein Sandberg, Cecilie Brinchmann, Jan E. Helseth, Eirik Rasmussen, Anne-Marie Lote, Knut Aamdal, Steinar Gaudernack, Gustav Kvalheim, Gunnar Langmoen, Iver A. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title | Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title_full | Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title_fullStr | Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title_full_unstemmed | Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title_short | Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma |
title_sort | therapeutic vaccination against autologous cancer stem cells with mrna-transfected dendritic cells in patients with glioblastoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755221/ https://www.ncbi.nlm.nih.gov/pubmed/23817721 http://dx.doi.org/10.1007/s00262-013-1453-3 |
work_keys_str_mv | AT vikmoeinarosland therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT nyakasmarta therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT mikkelsenbirtheviftrup therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT moemortencarstens therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT duetønnesenpaulina therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT susoelsemaritinderberg therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT sæbøelarssenstein therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT sandbergcecilie therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT brinchmannjane therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT helsetheirik therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT rasmussenannemarie therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT loteknut therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT aamdalsteinar therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT gaudernackgustav therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT kvalheimgunnar therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma AT langmoenivera therapeuticvaccinationagainstautologouscancerstemcellswithmrnatransfecteddendriticcellsinpatientswithglioblastoma |