***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: Cancer vaccine trials have failed to yield robust immune-correlated clinical improvements as observed in animal models , fueling controversy over the utility of human cancer vaccines . Therapeutic vaccination represents an intriguing additional therapy for glioblastoma multiforme ( GBM ; grade 4 glioma ) , which has a dismal prognosis and treatment response , but only early phase I vaccine trial results have been reported . Immune and clinical responses from a phase II GBM vaccine trial are reported here . IFN-gamma responsiveness was quantified in peripheral blood of 32 GBM patients given therapeutic dendritic cell vaccines .  Posttreatment times to tumor progression ( TTP ) and survival ( TTS ) were compared in vaccine responders and nonresponders and were correlated with immune response magnitudes . GBM patients ( 53 % ) exhibited > or=1.5-fold vaccine-enhanced cytokine responses . Endogenous antitumor responses of similar magnitude occurred in 22 % of GBM patients before vaccination . Vaccine responders exhibited significantly longer TTS and TTP relative to nonresponders . Immune enhancement in vaccine responders correlated logarithmically with TTS and TTP spanning postvaccine chemotherapy , but not with initial TTP spanning vaccination alone . This is the first report of a progressive correlation between cancer clinical outcome and T-cell responsiveness after therapeutic vaccination in humans and the first tracing of such correlation to therapeutically exploitable tumor alteration . As such , our findings offer unique opportunities to identify cellular and molecular components of clinical ly meaningful antitumor immunity in humans Purpose Dendritic cell (DC)-based tumor vaccination has rendered promising results in relapsed high- grade glioma patients . In the HGG-2006 trial ( EudraCT 2006 - 002881 - 20 ) , feasibility , toxicity , and clinical efficacy of the full integration of DC-based tumor vaccination into st and ard postoperative radiochemotherapy are studied in 77 patients with newly diagnosed glioblastoma . Patients and methods Autologous DC are generated after leukapheresis , which is performed before the start of radiochemotherapy . Four weekly induction vaccines are administered after the 6-week course of concomitant radiochemotherapy . During maintenance chemotherapy , 4 boost vaccines are given . Feasibility and progression-free survival ( PFS ) at 6 months ( 6mo-PFS ) are the primary end points . Overall survival ( OS ) and immune profiling , rather than monitoring , as assessed in patients ’ blood sample s , are the secondary end points . Analysis has been done on intent-to-treat basis . Results The treatment was feasible without major toxicity . The 6mo-PFS was 70.1 % from inclusion . Median OS was 18.3 months . Outcome improved significantly with lower EORTC RPA classification . Median OS was 39.7 , 18.3 , and 10.7 months for RPA classes III , IV , and V , respectively . Patients with a methylated MGMT promoter had significantly better PFS ( p = 0.0027 ) and OS ( p = 0.0082 ) as compared to patients with an unmethylated status . Exploratory “ immunological profiles ” were built to compare to clinical outcome , but no statistical significant evidence was found for these profiles to predict clinical outcome . Conclusion Full integration of autologous DC-based tumor vaccination into st and ard postoperative radiochemotherapy for newly diagnosed glioblastoma seems safe and possibly beneficial . These results were used to power the currently running phase IIb r and omized clinical trial In this Phase I/II trial , the patient 's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma .  Seven patients with glioblastoma and three patients with anaplastic glioma , ranging in age from 20 to 69 years , participated in this study . The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 3.7 times intradermally close to a cervical lymph node , and 3.2 times intratumorally via an Ommaya reservoir . The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunisation . There were two minor responses and four no-change cases evaluated by radiological findings . Dendritic cell vaccination elicited T-cell-mediated antitumour activity , as evaluated by the ELISPOT assay after vaccination in two of five tested patients . Three patients showed delayed-type hypersensitivity reactivity to the autologous tumour lysate , two of these had a minor clinical response , and two had an increased ELISPOT result . Intratumoral CD4 + and CD8 + T-cell infiltration was detected in two patients who underwent reoperation after vaccination . This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma OBJECT The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 ( Wilms tumor 1 ) gene product in patients with recurrent glioblastoma multiforme ( GBM ) . METHODS Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy .  In all patients , the tumors were resistant to st and ard therapy . Patients received intra-dermal injections of an HLA-A*2402-restricted , modified 9-mer WT1 peptide every week for 12 weeks . Tumor size , which was obtained by measuring the contrast-enhanced area on magnetic resonance images , was determined every 4 weeks . The responses were analyzed according to Response Evaluation Criteria in Solid Tumors ( RECIST ) 12 weeks after the initial vaccination . Patients who achieved an effective response continued to be vaccinated until tumor progression occurred . Progression-free survival and overall survival after initial WT1 treatment were estimated . RESULTS The protocol was well tolerated ; only local erythema occurred at the WT1 vaccine injection site . The clinical responses were as follows : partial response in 2 patients , stable disease in 10 patients , and progressive disease in 9 patients . No patient had a complete response . The overall response rate ( cases with complete or partial response ) was 9.5 % , and the disease control rate ( cases with complete or partial response as well as those in which disease was stable ) was 57.1 % . The median progression-free survival ( PFS ) period was 20.0 weeks , and the 6-month ( 26-week ) PFS rate was 33.3 % . CONCLUSIONS Although a small uncontrolled nonr and omized trial , this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response . Based on these results , further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted 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 BACKGROUND Although there have been significant advances in underst and ing the basic pathogenesis of glioblastoma multiforme , the median survival of patients has changed little in the past 25 years . Recent studies have suggested that immune modulation through dendritic cell ( DC ) vaccines may stimulate the immune system against tumor antigens and potentially increase survival . OBJECTIVE To determine whether the use of adjuvant vaccination with autologous DCs ( matured in situ after being loaded with tumor cell lysate derived from autologous refractory gliomas ) is safe , feasible , and beneficial for adult and pediatric patients with recurrent high- grade gliomas . METHODS The study design is a single-center , nonr and omized , open phase I clinical trial . A total of 20 patients with malignant gliomas will be enrolled preoperatively over 2 years . Patients will be given adjuvant vaccination with autologous DCs loaded with tumor lysate after maximal safe surgical resection . EXPECTED OUTCOMES Using topical imiquimod before vaccination , it is anticipated that the immune response in vaccinated patients and potentially Overall survival will be greater than that demonstrated in the literature . We anticipate that there will be minimal side effects ( minor dermatitis ) associated with this treatment . DISCUSSION In the current trial , we assess immune response , safety , and survival using a novel vaccine protocol developed in Belgium that seems to markedly increase survival of certain subjects . Nevertheless , larger r and omized clinical studies need to be performed to evaluate fully the efficacy of this therapy for both recurrent and newly diagnosed glioblastoma 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 . CONCL 
    Output:
    
Thus , our meta- analysis showed that DC immunotherapy markedly prolongs survival rates and progression-free time , enhances immune function , and improves the efficacy of the treatment of HGG patients