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

• Published in: Clinical cancer research 2022-02, Vol.28 (4), p.689-696
• Main Authors: Hu, Jethro L, Omofoye, Oluwaseun A, Rudnick, Jeremy D, Kim, Sungjin, Tighiouart, Mourad, Phuphanich, Surasak, Wang, Hongqiang, Mazer, Mia, Ganaway, Toni, Chu, Ray M, Patil, Chirag G, Black, Keith L, Shiao, Stephen L, Wang, Rongfu, Yu, John S
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - pathology; Cancer Vaccines; Cell Line; Dendritic Cells; Glioblastoma - pathology; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Recurrence, Local - drug therapy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-2867

Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥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 GBM 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 DC vaccine. For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, 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. In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC 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 GBM.