***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose : To assess the feasibility , safety , and toxicity of autologous tumor lysate – pulsed dendritic cell ( DC ) vaccination and toll-like receptor ( TLR ) agonists in patients with newly diagnosed and recurrent glioblastoma . Clinical and immune responses were monitored and correlated with tumor gene expression profiles . Experimental Design : Twenty-three patients with glioblastoma ( WHO grade IV ) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression . Gene expression profiling , immunohistochemistry , FACS , and cytokine bead arrays were performed on patient tumors and peripheral blood mononuclear cells . Results : DC vaccinations are safe and not associated with any dose-limiting toxicity . The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months , with a 1- , 2- , and 3-year survival rate of 91 % , 55 % , and 47 % , respectively . Patients whose tumors had mesenchymal gene expression signatures exhibited increased survival following DC vaccination compared with historic controls of the same genetic subtype . Tumor sample s with a mesenchymal gene expression signature had a higher number of CD3 + and CD8 + tumor-infiltrating lymphocytes compared with glioblastomas of other gene expression signatures ( P = 0.006 ) . Conclusion : Autologous tumor lysate – pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients . Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies . Clin Cancer Res ; 17(6 ) ; 1603–15 . © 2010 AACR Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)-engineered T cells .  Five patients experienced clinical regression of their cancers including 2 on-going responders . Beginning 1–2 days postinfusion , 3 patients ( # ’s 5 , 7 , and 8) experienced mental status changes , and 2 patients ( 5 and 8) lapsed into comas and subsequently died . Magnetic resonance imagining analysis of patients 5 and 8 demonstrated periventricular leukomalacia , and examination of their brains at autopsy revealed necrotizing leukoencephalopathy with extensive white matter defects associated with infiltration of CD3+/CD8 + T cells . Patient 7 , developed Parkinson-like symptoms , which resolved over 4 weeks and fully recovered . Immunohistochemical staining of patient and normal brain sample s demonstrated rare positively staining neurons with an antibody that recognizes multiple MAGE-A family members . The TCR used in this study recognized epitopes in MAGE-A3/A9/A12 . Molecular assays of human brain sample s using real-time quantitative-polymerase chain reaction , Nanostring quantitation , and deep-sequencing indicated that MAGE-A12 was expressed in human brain ( and possibly MAGE-A1 , MAGE-A8 , and MAGE-A9 ) . This previously unrecognized expression of MAGE-A12 in human brain was possibly the initiating event of a TCR-mediated inflammatory response that result ed in neuronal cell destruction and raises caution for clinical applications targeting MAGE-A family members with highly active immunotherapies Previous clinical trials of dendritic cell (DC)-based immunotherapy in patients with glioblastoma multiforme ( GBM ) have reported induction of systemic immune responses and prolonged survival . From 2003 to 2005 , we performed a clinical trial in which patients with malignant glioma underwent surgery for maximal cytoreduction followed by a 6-month 10-injection course of autologous DC-tumor vaccine therapy  , each injection containing 1 - 6 × 10(7 ) DC . Of the 17 treated patients ( 16 with World Health Organization grade IV and one with grade III glioma ) , eight ( 47.1 % ) had an initial transient elevation in aspartate aminotransferase (AST)/alanine aminotransferase ( ALT ) . Vaccination caused some tumor shrinkage and increased concentration of tumor-infiltrating CD8(+ ) lymphocytes . Median survival and 5-year survival were 525 days and 18.8 % , respectively , for 16 patients with grade IV glioma ( 381 days and 12.5 % for eight newly diagnosed ; 966 days and 25 % for eight relapsed patients ) compared to 380 days and 0 % for 63 historical control patients . We concluded that autologous DC-tumor immunotherapy benefits patients with malignant glioma but may cause transient but reversible elevation of serum AST/ALT levels PURPOSE To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma . EXPERIMENTAL DESIGN Twenty-four patients with recurrent malignant glioma ( 6 grade 3 and 18 grade 4 patients ) were evaluated in a phase I/II clinical study of dendritic cell therapy .  All patients were resistant to the st and ard maximum therapy .  The patient 's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor , plus interleukin 4 with or without OK-432 , and pulsed with an autologous tumor lysate . Dendritic cells were injected intradermally , or both intratumorally and intradermally every 3 weeks . RESULTS The protocol s were well tolerated with only local redness and swelling at the injection site in several cases . Clinical responses were as follows : 1 patient with partial response , 3 patients with minor response , 10 patients with stable disease , and 10 patients with progressive disease . The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation . The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only . Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination . The overall survival of patients with grade 4 glioma was 480 days , which was significantly better than that in the control group . CONCLUSIONS This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma .  Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients Background This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens ( TAA ) expressed on gliomas and overexpressed in their cancer stem cell population ( ICT-107 ) . Methods TAA epitopes included HER2 , TRP-2 , gp100 , MAGE-1 , IL13Rα2 , and AIM -2 . HLA-A1- and /or HLA-A2-positive patients with glioblastoma ( GBM ) were eligible .  Mononuclear cells from leukapheresis were differentiated into dendritic cells , pulsed with TAA peptides , and administered intradermally three times at two-week intervals . Results Twenty-one patients were enrolled with 17 newly diagnosed ( ND-GBM ) and three recurrent GBM patients and one brainstem glioma . Immune response data on 15 newly diagnosed patients showed 33 % responders . TAA expression by qRT-PCR from fresh-frozen tumor sample s showed all patient tumors expressed at least three TAA , with 75 % expressing all six . Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM -2 were observed , and a trend for longer survival was observed with gp100 and HER2 antigens . Target antigens gp100 , HER1 , and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2 + patients . A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection . At a median follow-up of 40.1 months , six of 16 ND-GBM patients showed no evidence of tumor recurrence . Median PFS in newly diagnosed patients was 16.9 months , and median OS was 38.4 months . Conclusions Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients . The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors The primary goal of this Phase I study was to assess the safety and bioactivity of tumor lysate-pulsed dendritic cell ( DC ) vaccination to treat patients with glioblastoma multiforme and anaplastic astrocytoma .  Adverse events , survival , and cytotoxicity against autologous tumor and tumor-associated antigens were measured . Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate . Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs . Vaccination with tumor lysate-pulsed DCs was safe , and no evidence of autoimmune disease was noted . Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay . Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-γ expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination . Using HLA-restricted tetramer staining , we identified a significant expansion in CD8 + antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1 , gp100 , and HER-2 after DC vaccination in four of nine patients . A significant CD8 + T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation . The median survival for patients with recurrent glioblastoma multiforme in this study ( n = 8) was 133 weeks . This Phase I study demonstrated the feasibility , safety , and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma . We demonstrate for the first time the ability of an active immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients Convection-enhanced delivery ( CED ) of cintredekin besudotox ( CB ) was compared with Gliadel wafers ( GW ) in adult patients with glioblastoma multiforme ( GBM ) at first recurrence . Patients were r and omized 2:1 to receive CB or GW . CB ( 0.5 microg/mL ; total flow rate 0.75 mL/h ) was administered over 96 hours via 2 - 4 intraparenchymal catheters placed after tumor resection . GW ( 3.85%/7.7 mg carmustine per wafer ; maximum 8 wafers ) were placed immediately after tumor resection . The primary endpoint was overall survival from the time of r and omization . Prestated interim analyses were built into the study design . Secondary and tertiary endpoints were safety and health-related quality -of-life assessment s.  From March 2004 to December 2005 , 296 patients were enrolled at 52 centers . Demographic and baseline characteristics were balanced between the 2 treatment arms . Median survival was 36.4 weeks ( 9.1 months ) for CB and 35.3 weeks ( 8.8 months ) for GW ( P = .476 ) . For the efficacy evaluable population , the median survival was 45.3 weeks ( 11.3 months ) for CB and 39.8 weeks ( 10 months ) for GW ( P = .310 ) . The adverse-events profile was similar in both arms , except that pulmonary embolism was higher in the CB arm ( 8 % vs 1 % , P = .014 ) . This is the first r and omized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients . There was no survival difference between CB administered via CED and GW . Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleuc 
    Output:
    
Immunotherapy was associated with a significantly longer OS and 2-year survival compared to conventional therapy .
CONCLUSION Immunotherapy may improve the survival of patients with GBM