Available Technology

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.

Investigators at the National Cancer Institute have found that beta-mannosylceramide (beta-ManCer) promotes immunity in an IFN-gamma independent mechanism. 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.

Patent Abstract: 

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.

Investigators at the National Cancer Institute have found that beta-mannosylceramide (beta-ManCer) promotes immunity in an IFN-gamma independent mechanism. 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.

Benefits 
Induces tumor immunity through a novel mechanism -Decreased possibility of neutralization by natural antibodies -Synergize with alpha-GalCer
Inventors: 

Masaki Terabe

Patent Number: 
PCTUS2011028024 US Application No. 13582,612 US
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