Regression of orthotopic brain tumors by cytokine-assisted tumor vaccines primed in the brain

Abstract

This study investigated the therapeutic effects of a rat glioma cell line, C6, that was engineered to secrete mouse GM-CSF (mGM-CSF) on intracerebral (i.c.) brain tumors. Significant antitumor immunity was induced in rats when the live or irradiated mGM-CSF-secreting tumor vaccine was implanted i.c. The antitumor activity was effective on small tumors and, to a lesser extent, on large tumors or tumors existing in vivo for a longer duration. Immunohistochemical analysis revealed cellular infiltrates (granulocytes, macrophages, and CD4⁺ and CD8⁺ T cells) at both the vaccine site and the tumor site, indicating that immune responses were similarly activated when tumor vaccine was inoculated in the brain, as at the subcutis. Additional studies demonstrated that the therapeutic effects of tumor vaccines on the large tumors or the long-existing tumors were enhanced by strategies such as increasing the dosage of tumor vaccines, using combined vaccines consisting of mGM-CSF and human interleukin-2, or combining tumor vaccine with herpes simplex virus thymidine kinase/ganciclovir treatment. All of the modified strategies yielded synergistic therapeutic effects on the large tumor burdens. The data presented herein suggest that cytokine gene therapy is highly promising for the treatment of i.c. gliomas.