A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

BACKGROUND Glioblastoma is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase 1 clinical trial utilizing an autologous dendritic cell vaccine pulsed with lysate derived from a glioblastoma stem-like cell line. METHODS Patients with newly diagnosed and recurrent glioblastoma were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, less than or equal to 4 mg dexamethasone daily dose, and Karnofsky score greater than or equal to 70. Vaccine treatment consisted of two phases: An induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed glioblastoma also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous dendritic cell vaccine. RESULTS For the 11 patients with newly diagnosed glioblastoma, median PFS was 8.75 months, and median OS was 20.36 months. For the 25 patients with recurrent glioblastoma, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS In this trial, treatment of newly diagnosed and recurrent glioblastoma with autologous dendritic cell vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well-tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of glioblastoma.