Technology Bundle ID
NCI-E-034-2010

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

Applications
Therapeutics
Lead Inventors
Masaki Terabe (NCI)
Co-Inventors
Ira Pastan ()
Development Status
Discovery (Lead Identification)
ICs
NCI

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.

Commercial Applications
  • Cancer therapeutics
  • Potent stimulator of NKT activity
Competitive Advantages
  • Induces tumor immunity through a novel mechanism
  • Decreased possibility of neutralization by natural antibodies
  • Synergize with alpha-GalCer

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