Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastomaReportar como inadecuado




Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cancer Immunology, Immunotherapy

, Volume 62, Issue 9, pp 1499–1509

First Online: 02 July 2013Received: 15 February 2013Accepted: 17 June 2013DOI: 10.1007-s00262-013-1453-3

Cite this article as: Vik-Mo, E.O., Nyakas, M., Mikkelsen, B.V. et al. Cancer Immunol Immunother 2013 62: 1499. doi:10.1007-s00262-013-1453-3

Abstract

BackgroundThe 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.

MethodsWe 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 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.

ResultsAutologous 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.

ConclusionThese findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.

KeywordsBrain cancer stem cell Tumorsphere Glioblastoma Dendritic cell Immunotherapy Autologous cell culture Electronic supplementary materialThe online version of this article doi:10.1007-s00262-013-1453-3 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor:

Fuente: https://link.springer.com/



DESCARGAR PDF




Documentos relacionados