***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 We evaluated the feasibility , safety , and immunogenicity of mature , peptide-pulsed dendritic cell ( DC ) vaccines administered by different routes . PATIENTS AND METHODS We performed a r and omized , phase I , dose-escalation study in 27 patients with metastatic melanoma receiving four autologous peptide-pulsed DC vaccinations .  Patients were r and omly assigned to an intravenous ( IV ) , intranodal ( IN ) , or intradermal ( ID ) route of administration ( ROA ) . For each route , primary end points were dose-limiting toxicity , maximum-tolerated dose , and T-cell sensitization . Sensitization was evaluated through tetramer staining , in vitro peptide recognition assays , and delayed-type hypersensitivity ( DTH ) responses . RESULTS Twenty-two ( 81.5 % ) of 27 patients completed all four vaccinations . Vaccinations were well tolerated ; a few patients exhibited grade 1 to 2 toxicities including rash , fever , and injection site reaction . All routes of administration induced comparable increases in tetramer-staining CD8 + T cells ( five of seven IV , four of seven IN , and four of six ID patients ) . However , the IN route induced significantly higher rates for de novo development of CD8 + T cells that respond by cytokine secretion to peptide-pulsed targets ( six [ 85.7 % ] of seven IN patients v two [ 33 % ] of six ID patients v none [ 0 % ] of six IV patients ; P = .005 ) and de novo DTH ( seven [ 87.5 % ] of eight IN patients v two [ 33.3 % ] of six ID patients v one [ 14.3 % ] of seven IV patients ; P = .01 ) compared with other routes . CONCLUSION Administration of this peptide-pulsed mature DC vaccine by IN , IV , or ID routes is feasible and safe . IN administration seems to result in superior T-cell sensitization as measured by de novo target-cell recognition and DTH priming , indicating that IN may be the preferred ROA for mature DC vaccines Purpose : Patients with glioblastoma have less than 15-month median survival despite surgical resection , high-dose radiation , and chemotherapy with temozolomide . We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells ( DC ) can extend survival and , in a separate study , that dose-intensified temozolomide ( DI-TMZ ) and adjuvant granulocyte macrophage colony-stimulating factor ( GM-CSF ) potentiate tumor-specific immune responses in patients with glioblastoma . Here , we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival ( PFS ) and overall survival ( OS ) . Experimental Design : Following st and ard-of-care , 11 patients with newly diagnosed glioblastoma  received DI-TMZ ( 100 mg/m2/d × 21 days per cycle ) with at least three vaccines of pp65 lysosome – associated membrane glycoprotein mRNA-pulsed DCs admixed with GM-CSF on day 23 ± 1 of each cycle . Thereafter , monthly DI-TMZ cycles and pp65-DCs were continued if patients had not progressed . Results : Following DI-TMZ cycle 1 and three doses of pp65-DCs , pp65 cellular responses significantly increased . After DI-TMZ , both the proportion and proliferation of regulatory T cells ( Tregs ) increased and remained elevated with serial DI-TMZ  cycles . Median PFS and OS were 25.3 months [ 95 % confidence interval ( CI ) , 11.0–∞ ] and 41.1 months ( 95 % CI , 21.6–∞ ) , exceeding survival using recursive partitioning analysis and matched historical controls . Four patients remained progression-free at 59 to 64 months from diagnosis . No known prognostic factors [ age , Karnofsky performance status ( KPS ) , IDH-1/2 mutation , and MGMT promoter methylation ] predicted more favorable outcomes for the patients in this cohort . Conclusions : Despite increased Treg proportions  following DI-TMZ , patients receiving pp65-DCs  showed long-term PFS and OS , confirming prior studies targeting cytomegalovirus in glioblastoma . Clin Cancer Res ; 23(8 ) ; 1898–909 . © 2017 AACR 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 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 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 Clinical and immunological analysis of the efficiency of combined immunotherapy with the use dendritic cells for the treatment of malignant glioma of the brain was carried out . Dendritic cells generated in the presence of granulocyte-macrophage CSF and IFN-α retain their functional characteristics in patients with gliomas , which suggests the possibility of their use for the treatment of malignant tumors ( glioma ) of the brain . Combined therapy using interferon-induced dendritic cells was associated with generation of antigen-specific immune response during vaccinations . The results indicate satisfactory tolerance of combined immunotherapy using dendritic cells and the absence of toxic side effects at the stage of adoptive immunotherapy and at the stage of vaccinations with dendritic cells . Clinical trials showed that vaccinations with dendritic cells included into combined immunotherapy improved the quality of life and survival of patients with malignant gliomas Glioblastoma ( GBM ) is the most com-mon and most lethal subtype of glioma and , despite advances , therapy prognosis re-mains poor with a median survival of ~15 months and a 2-year survival rate of 26 % [ 1 ] . St and ard therapy consists of tumor re-section , radiation and chemotherapy and a majority of patients receive antiangioge-netic therapy with the humanized anti-vas -cular endothelial growth factor monoclonal antibody bevacizumab as second-line ther-apy . In a r and omized Phase II clinical trial we use an individualized cancer immune therapy concept based on dendritic cells ( DC-CIT ) as add on to first-line therapy [ 2 ] . Our cancer vaccine AV0113 is comprised of two main components : Type 1 dendritic cells , that are characterized by the secretion of the immune regulatory molecule IL-12 to polarize the immune system towards a cy-tolytic immune response , are derived from the patient ’s monocytes and are pulsed with tumor antigens , that are extracted from 
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Compared to the control therapy group ( CT group ) , the DC group showed better OS and PFS without serious AEs .
Subgroup analysis showed that trials design ed as NRS obtained better results in the DC group in this study ; however , no specific subgroup regarding dosages , cycles or injection routes was found to be superior in the DC group compared to the CT group .
Conclusion DC vaccine can significantly improve OS and PFS , with acceptable toxicity , of HGG patients .