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MIP-1alpha Antagonizes the Effect of a GM-CSF-enhanced Subcutaneous Vaccine in a Mouse Glioma Model

MIP-1alpha Antagonizes the Effect of a GM-CSF-enhanced Subcutaneous Vaccine in a Mouse Glioma Model

Ulrich Herrlinger, Steffen Aulwurm, Herwig Strik, Simone Weit, Ulrike Naumann, Michael Weller

J Neurooncol. 2004 Jan;66(1-2):147-54.

PMID: 15015780

Abstract:

Subcutaneous vaccination using granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced glioma cells substantially prolongs survival in the mouse GL261 glioma model. To potentiate the efficacy of GM-CSF-based vaccination, syngeneic C57BL/6 mice bearing pre-implanted intracerebral GL261 gliomas were vaccinated twice subcutaneously with various combinations of glioma cells retrovirally engineered to release GM-CSF, interleukin (IL)-4 or macrophage inflammatory protein (MIP)-1alpha. More than 80% of the animals vaccinated with GM-CSF-secreting or GM-CSF- and IL-4-secreting cells were long-term survivors (> 120 days). Their survival was significantly prolonged compared with animals vaccinated with wild-type cells, which died after a median survival time of 30 days. The combination of IL-4 with GM-CSF did not provide a survival advantage over GM-CSF alone, regardless of whether the animals carried a small or large intracranial tumor load. Further, when the animals were vaccinated with a mixture of GM-CSF-, IL-4- and MIP-1alpha-secreting cells, the median survival was 37 days, and only 22% of the animals in this group were long-term survivors, similar to the vaccination effect of non-modified glioma cells. Thus, unexpectedly, the co-expression of MIP-1alpha, which was meant to attract T cells for stimulation by GM-CSF- and IL-4-stimulated dendritic cells, nullified the induction of an immune response against the GL261 glioma by a GM-CSF- and IL-4-expressing subcutaneous vaccine.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248674	MIP-1alpha from mouse			Price

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