Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial

Anticancer Res. 2020 Nov;40(11):6473-6484. doi: 10.21873/anticanres.14669.

Abstract

Background/aim: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy.

Patients and methods: Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients.

Results: The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients.

Conclusion: Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.

Keywords: Activated dendritic cell; HLA-A24; high-grade glioma; immunotherapy; phase II trial.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cell Polarity / immunology
  • Dendritic Cells / immunology*
  • Disease-Free Survival
  • Female
  • Glioma / drug therapy*
  • Glioma / immunology
  • Glioma / pathology
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-12 / genetics
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / pathology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • T-Lymphocytes / immunology
  • Vaccination / methods

Substances

  • Cancer Vaccines
  • IFNG protein, human
  • Interleukin-12
  • Interferon-gamma