Limits...
Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma.

Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tønnesen P, Suso EM, Sæbøe-Larssen S, Sandberg C, Brinchmann JE, Helseth E, Rasmussen AM, Lote K, Aamdal S, Gaudernack G, Kvalheim G, Langmoen IA - Cancer Immunol. Immunother. (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway. e.o.vik-mo@medisin.uio.no

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Survival of patient treated with DCs targeting GSCs compared to matched control patients treated with standard therapy. Comparison of the seven patients treated with DCs targeting GSCs compared to the ten controls matched by age, performance status, tumor volume, treatment modalities, and lack of corticosteroid treatment. a The vaccinated patients had a significantly longer progression-free survival (median of 694 days) compared to the matched controls (median 236 days; p = 0.0018, log-rank test). Two DC-treated patients had not developed recurrence (short straight bars). b The median overall survival was 759 days in the treated group compared to 585 days in the control group (p = 0.11, log-rank test). Three patients were still alive >1,000 days after surgery. c Descriptive data of the treated and control groups. Only PFS was significantly different between the two groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3755221&req=5

Fig3: Survival of patient treated with DCs targeting GSCs compared to matched control patients treated with standard therapy. Comparison of the seven patients treated with DCs targeting GSCs compared to the ten controls matched by age, performance status, tumor volume, treatment modalities, and lack of corticosteroid treatment. a The vaccinated patients had a significantly longer progression-free survival (median of 694 days) compared to the matched controls (median 236 days; p = 0.0018, log-rank test). Two DC-treated patients had not developed recurrence (short straight bars). b The median overall survival was 759 days in the treated group compared to 585 days in the control group (p = 0.11, log-rank test). Three patients were still alive >1,000 days after surgery. c Descriptive data of the treated and control groups. Only PFS was significantly different between the two groups

Mentions: Compared to the historical-matched controls, the groups were not significantly different in terms of important prognostic criteria. There was a trend toward larger tumor volumes in the controls and longer OS in the treated group (p = 0.1). The vaccinated patients had significantly longer PFS (median 694 days vs. 236 days, p = 0.0018, log-rank test, Fig. 3). Five of the treated patients developed tumor recurrence (at 10, 15, 17, 22, and 29 months, respectively). All patients in the matched control group experienced progression. Seven of these ten recurrences occurred earlier than the first recurrence in the vaccine group.Fig. 3


Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma.

Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tønnesen P, Suso EM, Sæbøe-Larssen S, Sandberg C, Brinchmann JE, Helseth E, Rasmussen AM, Lote K, Aamdal S, Gaudernack G, Kvalheim G, Langmoen IA - Cancer Immunol. Immunother. (2013)

Survival of patient treated with DCs targeting GSCs compared to matched control patients treated with standard therapy. Comparison of the seven patients treated with DCs targeting GSCs compared to the ten controls matched by age, performance status, tumor volume, treatment modalities, and lack of corticosteroid treatment. a The vaccinated patients had a significantly longer progression-free survival (median of 694 days) compared to the matched controls (median 236 days; p = 0.0018, log-rank test). Two DC-treated patients had not developed recurrence (short straight bars). b The median overall survival was 759 days in the treated group compared to 585 days in the control group (p = 0.11, log-rank test). Three patients were still alive >1,000 days after surgery. c Descriptive data of the treated and control groups. Only PFS was significantly different between the two groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3755221&req=5

Fig3: Survival of patient treated with DCs targeting GSCs compared to matched control patients treated with standard therapy. Comparison of the seven patients treated with DCs targeting GSCs compared to the ten controls matched by age, performance status, tumor volume, treatment modalities, and lack of corticosteroid treatment. a The vaccinated patients had a significantly longer progression-free survival (median of 694 days) compared to the matched controls (median 236 days; p = 0.0018, log-rank test). Two DC-treated patients had not developed recurrence (short straight bars). b The median overall survival was 759 days in the treated group compared to 585 days in the control group (p = 0.11, log-rank test). Three patients were still alive >1,000 days after surgery. c Descriptive data of the treated and control groups. Only PFS was significantly different between the two groups
Mentions: Compared to the historical-matched controls, the groups were not significantly different in terms of important prognostic criteria. There was a trend toward larger tumor volumes in the controls and longer OS in the treated group (p = 0.1). The vaccinated patients had significantly longer PFS (median 694 days vs. 236 days, p = 0.0018, log-rank test, Fig. 3). Five of the treated patients developed tumor recurrence (at 10, 15, 17, 22, and 29 months, respectively). All patients in the matched control group experienced progression. Seven of these ten recurrences occurred earlier than the first recurrence in the vaccine group.Fig. 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, University of Oslo, Oslo, Norway. e.o.vik-mo@medisin.uio.no

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus