Despite the advances in diagnosis and treatment (surgery +radiation +chemotherapy), median
      survival for patients with newly diagnosed brain glioblastoma multiform (GBM) is about one
      year, for recurrent GBM is about 4 months. Recently, immunotherapy has emerged as a novel
      treatment strategy for glioma with improving patient survival. Usually, processed tumor
      antigens from the patient's own tumor or a peptide vaccine is capable of producing an
      anti-glioma response. Our previous experiment revealed that the CD133+ tumor stem-like cells
      associated antigens could elicit highly intensive immune response against human malignant
      glioma , and in phase I study, we have confirmed that DC vaccine loaded with glioma stem-like
      cells associated antigens against malignant glioma in recurrent patients was of safety .

      Autologous DCs will be obtained from peripheral blood mononuclear cells (PBMCs) from each
      patient. Stem-like cells associated antigens (SAA) will be prepared with glioma stem-like
      cells that are harvested from patients with GBM and primary cultured and sorted
      flowcytometrically and then irradiated. Approximately 4 weeks will be required for vaccine
      production and the first vaccine administration. Each patient will receive an injection of
      DCs at his/her assigned dose once every week during the first 6 week. The dose of DCs is
      defined as 8~10×10^6.

      Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival
      benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately,
      at the present time the majority of clinical trials were in phase I that illustrated the
      safety. The efficacy of DCs against glioblastoma is still lack of sufficient randomized phase
      II study. According to our previous phase I study, here we designed this clinical trial in a
      triple-blind randomized manner to validate the efficacy of DCs vaccination.

      Recently，an exploratory randomized phase II clinical trial have been completed （Cancer
      immunology &immunotheapy ，2018，1677，1677-1688 ； PubMed ID: 30159779）， 43 GBM patients were
      randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline
      placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed.
      Participants were stratified into different molecular subgroups based on the mutation (MT)
      status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT).
      Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory
      molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed
      that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT
      promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1wild type (WT) TERTMT
      patients, DCV treatment significantly prolonged OS (p < 0.01) and PFS (p = 0.03) and
      increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low
      B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment.

      In the present study, IDH1WTTERTMT subgroups of GBM patients more responsive to GSC DCV-based
      specific active-immunotherapy. However，It is noted that IDH1WTTERTMTGBM patients was analysed
      in a cohort samples which are not randomlized and the present study population is too small
      to evaluate conclusively demographic criteria for entry and patient recruitment. the results
      of the present study should be confirmed in a random cohort of IDH1WTTERTMT GBM patients.
      Accordingly , we made some modifications to the original plan, and are currently recruiting
      new participants.