Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables

Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Friedrich Erhart [verfasserIn] Johanna Buchroithner [verfasserIn] René Reitermaier [verfasserIn] Katrin Fischhuber [verfasserIn] Simone Klingenbrunner [verfasserIn] Ido Sloma [verfasserIn] Dror Hibsh [verfasserIn] Renana Kozol [verfasserIn] Sol Efroni [verfasserIn] Gerda Ricken [verfasserIn] Adelheid Wöhrer [verfasserIn] Christine Haberler [verfasserIn] Johannes Hainfellner [verfasserIn] Günther Krumpl [verfasserIn] Thomas Felzmann [verfasserIn] Alexander M. Dohnal [verfasserIn] Christine Marosi [verfasserIn] Carmen Visus [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT

Übergeordnetes Werk:	In: Acta Neuropathologica Communications - BMC, 2013, 6(2018), 1, Seite 14
Übergeordnetes Werk:	volume:6 ; year:2018 ; number:1 ; pages:14

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s40478-018-0621-2

Katalog-ID:	DOAJ076591271

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245	1	0	\|a Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
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520			\|a Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.
650		4	\|a Glioblastoma multiforme
650		4	\|a Dendritic cell
650		4	\|a Cancer immunotherapy
650		4	\|a Immunology
650		4	\|a ELISPOT
653		0	\|a Neurology. Diseases of the nervous system
700	0		\|a Johanna Buchroithner \|e verfasserin \|4 aut
700	0		\|a René Reitermaier \|e verfasserin \|4 aut
700	0		\|a Katrin Fischhuber \|e verfasserin \|4 aut
700	0		\|a Simone Klingenbrunner \|e verfasserin \|4 aut
700	0		\|a Ido Sloma \|e verfasserin \|4 aut
700	0		\|a Dror Hibsh \|e verfasserin \|4 aut
700	0		\|a Renana Kozol \|e verfasserin \|4 aut
700	0		\|a Sol Efroni \|e verfasserin \|4 aut
700	0		\|a Gerda Ricken \|e verfasserin \|4 aut
700	0		\|a Adelheid Wöhrer \|e verfasserin \|4 aut
700	0		\|a Christine Haberler \|e verfasserin \|4 aut
700	0		\|a Johannes Hainfellner \|e verfasserin \|4 aut
700	0		\|a Günther Krumpl \|e verfasserin \|4 aut
700	0		\|a Thomas Felzmann \|e verfasserin \|4 aut
700	0		\|a Alexander M. Dohnal \|e verfasserin \|4 aut
700	0		\|a Christine Marosi \|e verfasserin \|4 aut
700	0		\|a Carmen Visus \|e verfasserin \|4 aut
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allfields	10.1186/s40478-018-0621-2 doi (DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff DE-627 ger DE-627 rakwb eng RC346-429 Friedrich Erhart verfasserin aut Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system Johanna Buchroithner verfasserin aut René Reitermaier verfasserin aut Katrin Fischhuber verfasserin aut Simone Klingenbrunner verfasserin aut Ido Sloma verfasserin aut Dror Hibsh verfasserin aut Renana Kozol verfasserin aut Sol Efroni verfasserin aut Gerda Ricken verfasserin aut Adelheid Wöhrer verfasserin aut Christine Haberler verfasserin aut Johannes Hainfellner verfasserin aut Günther Krumpl verfasserin aut Thomas Felzmann verfasserin aut Alexander M. Dohnal verfasserin aut Christine Marosi verfasserin aut Carmen Visus verfasserin aut In Acta Neuropathologica Communications BMC, 2013 6(2018), 1, Seite 14 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/article/31567993947f492daafe23f1e64695ff kostenfrei http://link.springer.com/article/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14
spelling	10.1186/s40478-018-0621-2 doi (DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff DE-627 ger DE-627 rakwb eng RC346-429 Friedrich Erhart verfasserin aut Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system Johanna Buchroithner verfasserin aut René Reitermaier verfasserin aut Katrin Fischhuber verfasserin aut Simone Klingenbrunner verfasserin aut Ido Sloma verfasserin aut Dror Hibsh verfasserin aut Renana Kozol verfasserin aut Sol Efroni verfasserin aut Gerda Ricken verfasserin aut Adelheid Wöhrer verfasserin aut Christine Haberler verfasserin aut Johannes Hainfellner verfasserin aut Günther Krumpl verfasserin aut Thomas Felzmann verfasserin aut Alexander M. Dohnal verfasserin aut Christine Marosi verfasserin aut Carmen Visus verfasserin aut In Acta Neuropathologica Communications BMC, 2013 6(2018), 1, Seite 14 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/article/31567993947f492daafe23f1e64695ff kostenfrei http://link.springer.com/article/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14
allfields_unstemmed	10.1186/s40478-018-0621-2 doi (DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff DE-627 ger DE-627 rakwb eng RC346-429 Friedrich Erhart verfasserin aut Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system Johanna Buchroithner verfasserin aut René Reitermaier verfasserin aut Katrin Fischhuber verfasserin aut Simone Klingenbrunner verfasserin aut Ido Sloma verfasserin aut Dror Hibsh verfasserin aut Renana Kozol verfasserin aut Sol Efroni verfasserin aut Gerda Ricken verfasserin aut Adelheid Wöhrer verfasserin aut Christine Haberler verfasserin aut Johannes Hainfellner verfasserin aut Günther Krumpl verfasserin aut Thomas Felzmann verfasserin aut Alexander M. Dohnal verfasserin aut Christine Marosi verfasserin aut Carmen Visus verfasserin aut In Acta Neuropathologica Communications BMC, 2013 6(2018), 1, Seite 14 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/article/31567993947f492daafe23f1e64695ff kostenfrei http://link.springer.com/article/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14
allfieldsGer	10.1186/s40478-018-0621-2 doi (DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff DE-627 ger DE-627 rakwb eng RC346-429 Friedrich Erhart verfasserin aut Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system Johanna Buchroithner verfasserin aut René Reitermaier verfasserin aut Katrin Fischhuber verfasserin aut Simone Klingenbrunner verfasserin aut Ido Sloma verfasserin aut Dror Hibsh verfasserin aut Renana Kozol verfasserin aut Sol Efroni verfasserin aut Gerda Ricken verfasserin aut Adelheid Wöhrer verfasserin aut Christine Haberler verfasserin aut Johannes Hainfellner verfasserin aut Günther Krumpl verfasserin aut Thomas Felzmann verfasserin aut Alexander M. Dohnal verfasserin aut Christine Marosi verfasserin aut Carmen Visus verfasserin aut In Acta Neuropathologica Communications BMC, 2013 6(2018), 1, Seite 14 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/article/31567993947f492daafe23f1e64695ff kostenfrei http://link.springer.com/article/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14
allfieldsSound	10.1186/s40478-018-0621-2 doi (DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff DE-627 ger DE-627 rakwb eng RC346-429 Friedrich Erhart verfasserin aut Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers. Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system Johanna Buchroithner verfasserin aut René Reitermaier verfasserin aut Katrin Fischhuber verfasserin aut Simone Klingenbrunner verfasserin aut Ido Sloma verfasserin aut Dror Hibsh verfasserin aut Renana Kozol verfasserin aut Sol Efroni verfasserin aut Gerda Ricken verfasserin aut Adelheid Wöhrer verfasserin aut Christine Haberler verfasserin aut Johannes Hainfellner verfasserin aut Günther Krumpl verfasserin aut Thomas Felzmann verfasserin aut Alexander M. Dohnal verfasserin aut Christine Marosi verfasserin aut Carmen Visus verfasserin aut In Acta Neuropathologica Communications BMC, 2013 6(2018), 1, Seite 14 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:6 year:2018 number:1 pages:14 https://doi.org/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/article/31567993947f492daafe23f1e64695ff kostenfrei http://link.springer.com/article/10.1186/s40478-018-0621-2 kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2018 1 14
language	English
source	In Acta Neuropathologica Communications 6(2018), 1, Seite 14 volume:6 year:2018 number:1 pages:14
sourceStr	In Acta Neuropathologica Communications 6(2018), 1, Seite 14 volume:6 year:2018 number:1 pages:14
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Acta Neuropathologica Communications
authorswithroles_txt_mv	Friedrich Erhart @@aut@@ Johanna Buchroithner @@aut@@ René Reitermaier @@aut@@ Katrin Fischhuber @@aut@@ Simone Klingenbrunner @@aut@@ Ido Sloma @@aut@@ Dror Hibsh @@aut@@ Renana Kozol @@aut@@ Sol Efroni @@aut@@ Gerda Ricken @@aut@@ Adelheid Wöhrer @@aut@@ Christine Haberler @@aut@@ Johannes Hainfellner @@aut@@ Günther Krumpl @@aut@@ Thomas Felzmann @@aut@@ Alexander M. Dohnal @@aut@@ Christine Marosi @@aut@@ Carmen Visus @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	746066465
id	DOAJ076591271
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ076591271</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309143915.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2018 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s40478-018-0621-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ076591271</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ31567993947f492daafe23f1e64695ff</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC346-429</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Friedrich Erhart</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. 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callnumber-first	R - Medicine
author	Friedrich Erhart
spellingShingle	Friedrich Erhart misc RC346-429 misc Glioblastoma multiforme misc Dendritic cell misc Cancer immunotherapy misc Immunology misc ELISPOT misc Neurology. Diseases of the nervous system Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
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topic_title	RC346-429 Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables Glioblastoma multiforme Dendritic cell Cancer immunotherapy Immunology ELISPOT
topic	misc RC346-429 misc Glioblastoma multiforme misc Dendritic cell misc Cancer immunotherapy misc Immunology misc ELISPOT misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc Glioblastoma multiforme misc Dendritic cell misc Cancer immunotherapy misc Immunology misc ELISPOT misc Neurology. Diseases of the nervous system
topic_browse	misc RC346-429 misc Glioblastoma multiforme misc Dendritic cell misc Cancer immunotherapy misc Immunology misc ELISPOT misc Neurology. Diseases of the nervous system
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title	Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
ctrlnum	(DE-627)DOAJ076591271 (DE-599)DOAJ31567993947f492daafe23f1e64695ff
title_full	Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
author_sort	Friedrich Erhart
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author_browse	Friedrich Erhart Johanna Buchroithner René Reitermaier Katrin Fischhuber Simone Klingenbrunner Ido Sloma Dror Hibsh Renana Kozol Sol Efroni Gerda Ricken Adelheid Wöhrer Christine Haberler Johannes Hainfellner Günther Krumpl Thomas Felzmann Alexander M. Dohnal Christine Marosi Carmen Visus
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title_sort	immunological analysis of phase ii glioblastoma dendritic cell vaccine (audencel) trial: immune system characteristics influence outcome and audencel up-regulates th1-related immunovariables
callnumber	RC346-429
title_auth	Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
abstract	Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.
abstractGer	Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.
abstract_unstemmed	Abstract Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.
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title_short	Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables
url	https://doi.org/10.1186/s40478-018-0621-2 https://doaj.org/article/31567993947f492daafe23f1e64695ff http://link.springer.com/article/10.1186/s40478-018-0621-2 https://doaj.org/toc/2051-5960
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It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via “danger signals”. The recent phase II “GBM-Vax” trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel’s effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel’s general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further – with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glioblastoma multiforme</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic cell</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cancer immunotherapy</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immunology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ELISPOT</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neurology. 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Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables

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