The synergistic effect of combination therapy with a single dose of α-galactosylceramide followed b and sub-therapeutic levels of TNF can be exploited to safely combat cancer without the typical side effects of TNF treatment.
Summary of the Invention
Tumor necrosis factor (TNF) is cytotoxic to tumor cells but treatment with TNF is not possible due to its systemic side effects such as hypotension, fever and headache. α-Galactosylceramides have previously been shown to exhibit anti-tumor and immune-stimulating activity in pre-clinical animal models, but failed to display sufficient anti-tumor activity in clinical studies.
VIB researchers have found that α-galactosylceramide specifically activates natural killer cells and induces a selective increase of the anti-tumor effect of TNF. Low levels of TNF used are display synergy with α-galactosylceramide treatment and result in surprising tumor regression of various tumor cancer models. Furthermore, no significant cytotoxic effects on normal cells were observed in animals subjected to the combination treatment.