Background: Glioblastoma (GBM) is a poor prognosis malignant grade IV glioma. After surgical resection, standard therapy consists of concomitant radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Multiple phase I/II trials and at least 3 meta-analysis showed improved survival (OS) and progression free survival (PFS) with DC vaccination in High-grade gliomas (HGGs) patients (pts). In pts developing antitumor immunity, DC vaccination increases the amount of intratumoral activated cytotoxic T lymphocytes and decreases the number of FoxP3 positive regulatory T cells. Based on these data we have developed a phase II protocol with DC vaccine concomitant to standard RT-CT in pts who have undergone radical surgery for GBM. Methods: This is a single-arm, monocentric, phase II trial of a DC vaccination integrated to standard therapy in resected GBM pts. All pts receive a dendritic cell vaccine loaded with autologous tumor homogenate for up to one year. The vaccine administration starts at the end of the RT-CT (Induction Phase) and then is alternated to TMZ cycles (Maintenance Phase). Primary end points are PFS and safety, among secondary end points there are the in vitro (Elispot, Plasma Cytokines, Tumor tissue analysis) and in vivo (DTH skin test) Immune response evaluations. A Simon's two-stage design has been used for the sample size calculation. In the first stage, 9 patients have been accrued and a total of 28 patients will be enrolled at the end of the second step. Results: From July 2021, the 9 pts of the first step has been enrolled, 4 females and 5 males with median age of 58 years. Five pts had no MGMT mutation. All 9 pts concluded the induction phase. To November 2022 four pts have progressed with a median PFS, from the date of leukapheresis, of 6.5 months (3.2-NE). DTH test became positive in 5 out of 9 evaluable pts. Median OS from the date of surgery was 11 months. No gr 3-4 vaccine related toxicities have been observed and gr 1-2 toxicities were mostly due to local skin reactions. Conclusions: On the basis of the results described above and the vaccine favorable toxicity profile the Study Team decided to proceed with the second step. Clinical trial information: EUCTR220-003755-15.