Effects of irradiated tumor vaccine and infusion of granulocyte-macrophage colony-stimulating factor and interleukin-12 on established gliomas in rats

Jin Cherng Chen, Yun Chen, Jiann Ming Wu, Yen Hao Su, Kuo Feng Tai, Sheng Hong Tseng

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) infused into the injection site of irradiated tumor vaccine (TV) as therapy for gliomas. Methods: Rats with subcutaneous RT-2 gliomas were treated with irradiated TV and/or subcutaneous infusion of GM-CSF and/or IL-12 via osmotic minipump 5 days after tumor-cell inoculation. Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity were analyzed to investigate immune responses. Rats with intracerebral gliomas were treated with irradiated TV and infused GM-CSF/IL-12 3 days after tumor-cell inoculation. Tumor growth rates and animal survival were followed. Survivors were re-challenged with wild-type RT-2 cells subcutaneously or intracerebrally to study long-term anti-tumor immunity. Results: Rats with subcutaneous gliomas treated with GM-CSF and IL-12 or TV plus GM-CSF or IL-12 did not have increased survival rate (P > 0.2), but did have prolonged survival time (P < 0.05); in contrast, rats treated with TV plus GM-CSF/IL-12 had increased survival rate (P < 0.05) and prolonged survival time (P < 0.05) compared with controls. These treatment strategies showed enhanced CTL and NK cell activities. Rats with intra-cerebral gliomas treated with TV plus GM-CSF/IL-12 did not have increased survival rate (P = 0.11), but did have prolonged survival time (P < 0.0001). Survivors in each group were re-challenged with wild-type RT-2 cells, and all had long-term survival. Conclusions: Irradiated TV plus continuous localized infusion of GM-CSF/IL-12 may induce a tumor-specific anti-tumor immune response on established subcutaneous or intra-cerebral gliomas, and such a treatment strategy deserves consideration as adjuvant treatment for glioma.

Original languageEnglish
Pages (from-to)873-883
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume55
Issue number7
DOIs
Publication statusPublished - Jul 1 2006
Externally publishedYes

    Fingerprint

Keywords

  • Glioma
  • GM-CSF
  • IL-12
  • Immunotherapy
  • Tumor vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this