Immuno Gene Therapy of Rat Brain Tumors with interferon-gamma transfected glioma cells

Immunotherapy is a new promising approach in cancer treatment. In the future, it will hopefully offer an alternative to existing brain tumors treatments, which are unable to cure. We have established an experimental, low immunogenic, brain tumor model in the rat. We have increased tumor cell immunogenicity with mutagen treatment or transfection of IFN-g. Mutagen treated glioma cells (tum-) could cross protect for subsequent challenge of wild type tumor cells. Immunization with tum- cells pre-incubated with IFN-g could also reject wild type tumor after tumor grafting. Lymphocyte populations in draining lymph nodes after tum- immunization showed the number of CD8+ T cells to increase fastest and strongest. IFN-g and TNF-a induction was stronger (in the CD8+ T cell compartment), while IL-10 was weaker (in the CD4+ T cell compartment) after tum- immunization as compared to control immunization.

Peripheral immunizations with IFN-g transfected glioma cells after tumor grafting, were able to induce total tumor rejection of 37 and 72% with the N32 and N29 glioma, respectively. B7 or IL-7 transfected tumor cells could also cure but were less effective. Analysis of tumor infiltrating leucocytes in N32-IFN-g immunized as compared to control animals, showed a significant higher infiltration density in CD8+ and CD4+ T cells, as well as NK cells. CD8+ T cells from tumors immunized with N32-IFN-g also had increased LFA-1 expression. CD25 expression was similar between immunization groups, with CD25low expression in both CD4+ and CD8+ T cells, as well as CD25high expression in a population of CD4+ T cells.