Biomaterial-based vaccine induces regression of established intracranial glioma in rats

Pharm Res. 2011 May;28(5):1074-80. doi: 10.1007/s11095-010-0361-x. Epub 2011 Jan 12.

Abstract

Purpose: The prognosis for glioma patients is poor, and development of new treatments is critical. Previously, we engineered polymer-based vaccines that control GM-CSF, CpG-oligonucleotide, and tumor-lysate presentation to regulate immune cell trafficking and activation, which promoted potent immune responses against peripheral tumors. Here, we extend the use of this system to glioma.

Methods: Rats were challenged with an intracranial injection of glioma cells followed (1 week) by administration of the polymeric vaccine (containing GM-CSF, CpG, and tumor-lysate) in the tumor bed. Control rats were treated with blank matrices, matrices with GM-CSF and CpG, or intra-tumoral bolus injections of GM-CSF, CpG, and tumor lysate. Rats were monitored for survival and tested for neurological function.

Results: Survival studies confirmed a benefit of the polymeric vaccine as 90% of vaccinated rats survived for > 100 days. Control rats exhibited minimal benefit. Motor tests revealed that vaccination protected against the loss of forelimb use produced by glioma growth. Histological analysis quantitatively confirmed a robust and rapid reduction in tumor size. Long-term immunity was confirmed when 67% of survivors also survived a second glioma challenge.

Conclusions: These studies extend previous reports regarding this approach to tumor therapy and justify further development for glioma treatment.

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cancer Vaccines / therapeutic use*
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunotherapy*
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / therapeutic use
  • Rats
  • Rats, Sprague-Dawley

Substances

  • CPG-oligonucleotide
  • Cancer Vaccines
  • Oligodeoxyribonucleotides
  • Granulocyte-Macrophage Colony-Stimulating Factor