Immune-based treatments for central nervous system
gliomas have traditionally lagged behind those of more immunogenic
tumors such as
melanoma. The relative paucity of defined
glioma-associated
antigens that can be targeted by the immune system may partially account for this situation.
Antigens present on
melanomas have been extensively characterized, both in humans and in murine preclinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts,
malignant melanomas and
gliomas, have been shown in humans to share common
antigens at the
RNA level. However, little is known concerning whether
gliomas can be targeted by immune-based strategies that prime T cells to
epitopes from
melanoma-associated
antigens (MAAs). In this study, we provide evidence that two common murine
glioma cell lines (GL26 and GL261) express the
melanoma antigens gp100 and
tyrosinase-related
protein 2 (TRP-2). To understand the immunogenicity of murine
gliomas to CD8(+) T cells, we examined the ability of a MAA-specific CTL cell line to lyse the
glioma cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals harboring
gliomas. Both
glioma cell lines were lysed by a human gp100-specific CTL cell line in vitro. Mice harboring s.c. GL26
gliomas possessed TRP-2-specific CD8(+) T cells, providing further evidence that these
gliomas express the
protein products in the context of MHC class I. Furthermore, MAA
peptide-pulsed dendritic cells could prime T cells that specifically recognize GL26
glioma cells in vitro. Lastly, mice that were prevaccinated with human gp100 and TRP-2
peptide-pulsed dendritic cells had significantly extended survival when challenged with
tumor cells in the brain, resulting in >50% long-term survival. These results suggest that shared MAAs on
gliomas can be targeted immunotherapeutically, pointing the way to a new potential treatment option for patients with
malignant gliomas.