Natural killer T (NKT) cells, a unique subpopulation of T cells with immunomodulatory properties involved in a broad range of immune responses, are stimulated by glycolipid antigens, particularly by alpha-galactosylceramide (alfa-GalCer). Due to the exceptional potency of alfa-GalCer on NKT cell stimulation, which simultaneously induces the expression of Th1 and Th2 cytokines, different side effects are obtained in vivo. As NKT stimulation is a basic mechanism of immune activation, new compounds are intended to achieve selective modulation of Th2 or Th1 cytokine release and improving in vivo profiles.
The MCS group has developed several families of non-glycosidic analogues of alfa-GalCer. Some members of these families are more versatile modulators of cytokine production and have a longer life than alfa-GalCer. They show potent activity in vitro to stimulate NKT cell proliferation by inducing cytokine release both in vitro and in vivo (in mice) with a highly efficient and potent selective Th1 (IFN gamma) cytokine release. This has also been experimentally proved in a B16 melanoma model in mice, preventing lung metastases at the nanogram scale.
Due to the role of NKT cells, these compounds can have application in cancer immunotherapy, for the cooperative stimulation of the patient immune system, and as vaccine adjuvants in autoimmune diseases or infections.