Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that locate in peripheral organs. It has been thought that a systemic immune response does not play a role in regression of central nervous system (CNS)
tumors, because the CNS is an immunologically privileged site. However, recent advances in immunology have led to the possibility of
immunotherapy using peripheral DCs against CNS
tumors. Here, we investigated whether DCs pulsed with
tumor extract could induce an antitumor effect against
malignant glioma. Furthermore, we also investigated whether the antitumor effect become higher by pulsation with
tumor extract-
liposome complex, compared to pulsation with
tumor extract alone. As a
liposome, we used cationic small
unilamellar vesicles composed of
N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG),
dilauroylphosphatidylcholine (DLPC), and
dioleoylphosphatidylethanolamine (DOPE) in a molar ratio of 1:2:2. After intracerebral inoculation of mouse
malignant glioma GL261 cells into syngeneic C57BL/6 mice, DCs pulsed with extract from the
glioma cells by sonication were administered intraperitoneally thrice weekly on days 7, 14 and 21.
Tumor growth inhibition was evaluated by measuring the
tumor size 1 month after the
tumor inoculation. The group treated with DCs pulsed by
tumor extract was inhibited in
tumor progression compared with the control non-pulsed DCs group, and the group treated with DCs pulsed by
tumor extract and
liposomes showed substantial
tumor volume reductions in all the mice. Among the mice, there 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
malignant glioma.