MIP-1alpha antagonizes the effect of a GM-CSF-enhanced subcutaneous vaccine in a mouse glioma model

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