Dendritic cells pulsed with tumor extract-cationic liposome complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that locate in peripheral organs. It has been thought that a systemic immune re sponse does not play a role in regression of central nervous system (CNS) t umors, because the CNS is an immunologically privileged site. However, rece nt advances in immunology have led to the possibility of immunotherapy usin g peripheral DCs against CNS tumors. Here, we investigated whether DCs puls ed with tumor extract could induce an antitumor effect against malignant gl ioma. Furthermore, we also investigated whether the antitumor effect become higher by pulsation with tumor extract-liposome complex, compared to pulsa tion with tumor extract alone. As a liposome, we used cationic small unilam ellar vesicles composed of N-(alpha -trimethylamnionioacetyl)-didodecyl-D-g lutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleoyl phosphatidylethanolamine (DOPE) in a molar ratio of 1:2:2. After intracereb ral inoculation of mouse malignant glioma GL261 cells into syngeneic C57BL/ 6 mice, DCs pulsed with extract from the glioma cells by sonication were ad ministered intraperitoneally thrice weekly on days 7, 14 and 21. Tumor grow th inhibition was evaluated by measuring the tumor size I month after the t umor inoculation. The group treated with DCs pulsed by tumor extract was in hibited in tumor progression compared with the control non-pulsed DCs Group , and the group treated with DCs pulsed by tumor extract and liposomes show ed substantial tumor volume reductions in all the mice. Among the mice, the re were several with no visible masses in their brains. Immunohistochemical study showed that the CD8-positive cytotoxic T cells (CTLs) were strongly recognized among the almost disappearing tumor cells of pulsed DCs groups. The CTLs showed a specific antitumor activity for GL261 mouse glioma cells. These findings indicated that DCs pulsed with tumor extract and liposomes might play an important role in the activation of an immune response in mal ignant glioma.