Etiology and Pathogenesis > Granulocyte-macrophage colony-stimulating factor | Treatment > Immunotherapy

Abstract

MIP-1α 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 and Michael Weller

Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of T¨ubingen, T¨ubingen, Germany

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-CSFbased 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)-1α. 
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 vaccinated with a mixture of GM-CSF-, IL-4- and MIP-1α-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-1α, 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

Key words: animal model, glioma, GM-CSF, MIP-1α, vaccination therapy

© 2004 Kluwer Academic Publishers. Printed in the Netherlands.

Source: http://journals.kluweronline.com/article.asp?PIPS=5149476