Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma

Amy B. Heimberger, Laura E. Crotty, Gary E. Archer, Roger E. McLendon, Allan Friedman, Glenn Dranoff, Darell D. Bigner, John H. Sampson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-βs, immunosuppressive cytokines secreted by human gliomas. Systemic vaccination of mice with DCs pulsed with tumor homogenate followed by intracranial tumor challenge produced a >160% increase in median survival (p=0.016) compared with mice vaccinated with PBS or unpulsed DCs (p=0.083). Fifty percent of mice treated with pulsed DCs survived long-term. Immunologic memory was demonstrated by survival of mice rechallenged with tumor. Both cell-mediated and humoral immunity was induced. On histological examination only focal areas of demyelination at the tumor implantation site were present. There was no evidence that autoimmune encephalomyelitis was induced by DC vaccination. Therefore, in a murine model, vaccination with DCs pulsed with glioma tumor homogenate is a safe and effective therapy against a syngeneic glioma located in the immunologically privileged central nervous system (CNS). Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)16-25
Number of pages10
JournalJournal of Neuroimmunology
Volume103
Issue number1
DOIs
StatePublished - Feb 1 2000
Externally publishedYes

Keywords

  • Central nervous system (CNS)
  • Dendritic cells
  • Encephalomyelitis
  • Glioma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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