Development of systemic immunity to glioblastoma multiforme using tumor cells genetically engineered to express the membrane-associated isoform of macrophage colony-stimulating factor.

摘要: We investigated the ability of Fischer rat T9 glioblastoma cells transduced with cDNA genes for secreted (s) or membrane-associated (m) isoform M-CSF to elicit an antitumor response when implanted into syngeneic animals. Intracranial (i.c.) implantation 1 x 10(5) expressing mM-CSF (T9/mM-CSF) resulted in 80% tumor rejection. Electron microscopy T9/mM-CSF site, 2-4 days postimplantation, showed marked infiltration by macrophages, many which were physical contact cells. Animals that rejected resistant i.c. rechallenge cells, but not MadB106 breast adenocarcinoma suggesting T9-specific immunity can be generated within brain via endogenous APCs. injection parental T9, vector control (T9/LXSN), secreting (T9/sM-CSF) was 100% fatal. Subcutaneous 10(7) T9/sM-CSF, T9/LXSN, progressive tumors. In contrast, injected s.c. destroyed 7-10 and animals developed systemic Passive transfer CD3+ T from spleens immune rats naive recipients transferred glioma-specific immunity. vitro, splenocytes T9/mM-CSF-immunized specifically proliferated various glioma stimulator However, only marginal cell-mediated cytotoxicity observed these a CTL assay against target regardless restimulation immunization viable effective eradicating