Melanoma patients often develop
brain metastases despite effective systemic
immunotherapy against
melanoma. We have attempted to establish a mouse model to develop strategies to combat this problem. Immunization of C57BL/6 (H-2b) mice with a combination of the syngeneic G3.12/BM2
melanoma (a B16 subclone) and the allogeneic Cloudman-S91
melanoma was effective in preventing the growth of 10,000 viable, s.c. injected G3.12 cells in 93% of the mice. Irradiated whole
tumor cells pretreated with
gamma-interferon for 2 days were most effective. A nonspecific adjuvant (DETOX) was injected routinely together with the
tumor cells. Active immunization with 2 different doses of irradiated
melanoma cells (1 x 10(5) or 2.5 x 10(6) cells/injection x 5
injections) protected against intracerebral challenge with 200 live G3.12 cells in 69% of the mice. This challenge caused the death of all control mice within 30 days. T-cell-mediated,
tumor-specific cytotoxicity against G3.12
melanoma was demonstrated in the spleen of immunized mice. Histological observations in the brain, 80 days after
tumor challenge, indicated complete eradication of the
melanoma, but although CD4+ and CD8+ T-cells and macrophages were present, their number was low.
Gliosis was present in both immunized and control animals. Thus, in this murine
melanoma model syngeneic mice were protected from death by s.c. and intracerebrally inoculated
tumor cells if pretreated with a sufficient number of irradiated syngeneic and allogeneic
melanoma cells and an
immunological adjuvant. Whether this regimen can treat established
tumors of the brain, alone or in combination, is uncertain. Yet its success suggests that the "blood-brain barrier" impeding immunity to
tumors may not be absolute.