Effects of irradiated tumor vaccine and infusion of granulocyte-macrophage colony-stimulating factor and interleukin-12 on established gliomas in rats
Journal
Cancer Immunology, Immunotherapy
Journal Volume
55
Journal Issue
7
Pages
873-883
Date Issued
2006
Author(s)
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. ? Springer-Verlag 2005.
Subjects
Glioma; GM-CSF; IL-12; Immunotherapy; Tumor vaccine
Other Subjects
recombinant granulocyte macrophage colony stimulating factor; recombinant interleukin 12; tumor vaccine; animal cell; animal experiment; animal model; antineoplastic activity; article; cancer immunotherapy; cancer survival; cellular immunity; comparative study; controlled study; cytotoxic T lymphocyte; drug effect; experimental neoplasm; glioma; immune response; inoculation; irradiation; long term care; natural killer T cell; nonhuman; osmotic minipump; priority journal; rat; survival rate; survival time; wild type; Animals; Brain Neoplasms; Cancer Vaccines; Drug Screening Assays, Antitumor; Glioma; Granulocyte-Macrophage Colony-Stimulating Factor; Infusion Pumps, Implantable; Infusions, Parenteral; Injections, Intralesional; Interleukin-12; Killer Cells, Natural; Neoplasm Transplantation; Rats; Rats, Inbred F344; Recombinant Proteins; Subcutaneous Tissue; T-Lymphocytes, Cytotoxic
Type
journal article