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 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.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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-013-1453-3) contains supplementary material, which is available to authorized users.
Highlights
Glioblastoma is the most common primary brain tumor and has one of the poorest prognoses of all cancers
Temozolomide has recently been shown to increase progression-free survival (PFS) in a selected group by 1.9 months and median overall survival (OS) by 2.5 months compared to radiotherapy alone [1], the prognosis for glioblastoma patients has improved very little since post-operative radiotherapy became the standard of care four decades ago
Primary tumorsphere cell cultures retain the genotype of the tumor of origin [27, 32] and maintain the ability to initiate a tumor with patient-specific characteristics upon orthotopic grafting [27, 32, 33]
Summary
Glioblastoma is the most common primary brain tumor and has one of the poorest prognoses of all cancers. The sphere-forming assay has subsequently been shown to be a robust method for the isolation and expansion of glioblastoma stem cells (GSCs) [6, 7]. These cells share a number of properties with stem cells from the normal adult human brain [8], which have the ability to differentiate into multi-lineage progeny, and have the capacity to propagate the tumor upon serial xenografting [6, 9,10,11], fulfilling the criteria for classification as CSCs. The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
