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Effects of combined granulocyte-macrophage
colony-stimulating factor (GM-CSF), interleukin-2, and interleukin-12 based
immunotherapy against intracranial glioma in the rat
Jean WC, Spellman SR, Wallenfriedman MA, Flores CT, Kurtz BP, Hall WA, Low WC
Department of Neurosurgery, University of Minnesota, Minneapolis,
MN 55455, USA.
Cytokines play a major role in the regulation of the immune system.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be
useful for immunotherapy against glioma because it can stimulate dendritic cells
to present tumor antigen.
Interleukin-2 (IL-2) is involved in T-cell expansion, and interleukin-12 (IL-12)
drives the T-helper cell type I response.
Previous studies have shown that each of these cytokines alone can induce the
regression of tumor cells.
In the present study we postulated that peripheral infusion of GM-CSF along with
either IL-2 or IL-12 and irradiated tumor cells can lead to increased survival
from 9L brain tumors.
9L gliosarcoma cells (10(6)) were implanted in the brains of syngeneic Fischer
344 rats.
Osmotic minipumps were utilized for subcutaneous, continuous delivery of GM-CSF,
either alone or with IL-2 or IL-12.
Irradiated 9L cells were injected subcutaneously at various time points during
treatment.
Delayed-type hypersensitivity (DTH) and immunohistological analysis were used to
further characterize the anti-tumor response.
Treatment with GM-CSF and irradiated tumor cells led to an increase in survival
rate in rats with intracranial 9L tumors when compared to untreated
animals.
The addition of IL-2 or IL-12 to the GM-CSF/tumor cell therapy further increased
the survival rate up to 90%.
The anti-tumor response was associated with vigorous DTH against 9L cells and
increased infiltration of CD4+ and CD8+ lymphocytes into the tumor.
These results suggest that the combined infusion of GM-CSF and other cytokines
may be effective adjuvants in treating brain tumors.
PMID: 15015768 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15015768
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