A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma

J Clin Neurosci. 2011 Aug;18(8):1048-54. doi: 10.1016/j.jocn.2010.11.034. Epub 2011 Jun 28.

Abstract

Previous clinical trials of dendritic cell (DC)-based immunotherapy in patients with glioblastoma multiforme (GBM) have reported induction of systemic immune responses and prolonged survival. From 2003 to 2005, we performed a clinical trial in which patients with malignant glioma underwent surgery for maximal cytoreduction followed by a 6-month 10-injection course of autologous DC-tumor vaccine therapy, each injection containing 1-6×10(7) DC. Of the 17 treated patients (16 with World Health Organization grade IV and one with grade III glioma), eight (47.1%) had an initial transient elevation in aspartate aminotransferase (AST)/alanine aminotransferase (ALT). Vaccination caused some tumor shrinkage and increased concentration of tumor-infiltrating CD8(+) lymphocytes. Median survival and 5-year survival were 525 days and 18.8%, respectively, for 16 patients with grade IV glioma (381 days and 12.5% for eight newly diagnosed; 966 days and 25% for eight relapsed patients) compared to 380 days and 0% for 63 historical control patients. We concluded that autologous DC-tumor immunotherapy benefits patients with malignant glioma but may cause transient but reversible elevation of serum AST/ALT levels.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Brain Neoplasms / immunology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Cancer Vaccines
  • Dendritic Cells / immunology*
  • Female
  • Follow-Up Studies
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioma / immunology
  • Glioma / mortality
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Postoperative Period
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD
  • Cancer Vaccines
  • Glial Fibrillary Acidic Protein