Cancer Therapeutic based on Stimulation of Natural Killer T-cell Anti-tumor Activity

Natural killer T cells (NKT) are a unique lymphocyte population that has T-cell and NK cell functional properties in order to rapidly elicit an immune response.  alpha-galactosylceramide (alpha-GalCer) is a potent NKT stimulator and induces of IFN-gamma release to promote immunity against tumors and infectious agents.  Humans have natural antibodies against alpha-galactose, which may be one of the reasons why the human clinical trials of alpha-GalCer or KRN7000 were not very successful.

Beta-ManCer is a new class of NKT agonist that induces immune responses alone, through nitric oxide and TNF-alpha-dependent mechanisms, or synergistically with alpha-GalCer to enhance alpha-GalCer''s efficacy.  Since beta-ManCer does not have alpha-galactose, which can be neutralized by natural antibodies, patients could be treated with multiple doses without negative side effects associated with the loss of IFN-gamma production.  Hence, beta-ManCer is a promising anti-cancer treatment either alone or in combinatorial therapies with alpha-GalCer to selectively induce immune responses.