Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of neuro-oncology, 2004-01, Vol.66 (1/2), p.147-154

Ort / Verlag

New York: Springer Nature B.V

Erscheinungsjahr

2004

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.