Immunotherapy – NKT cell activators

Invariant natural killer T (iNKT) cells, involved in a broad range of immune responses, are stimulated by glycolipid antigens, particularly by alpha-galactosylceramide (α-GalCer). Due to the exceptional potency of α-GalCer and that it simultaneously induces the expression of Th1 and Th2 cytokines, with opposite functions, new compounds are intended to achieve selective modulation of Th2 or Th1 cytokine release.

The MCS group has developed a new family of non-glycosidic analogs of α-GalCer with an aminocyclitol, as galactose mimetic, bonded to a phytoceramide by an amino functional group. These aminocyclitol derivatives are more versatile modulators of cytokine production and have longer life than α-galactosylceramide. They show potent activity to stimulate iNKT cell proliferation by inducing cytokine release both in vitro and in vivo (in mice) with a highly efficient and potent Th1 (IFNγ) antitumoral response.

This has been proved in a B16 melanoma model, preventing lung metastases at nanogram scale. Due to the role of iNKT cells, these compounds can have application as vaccine adjuvants in autoimmune diseases or infections and in cancer immunotherapy for cooperative stimulation of the patient immune system.

This work is developed in collaboration with University of Melbourne (Australia), Monash University (Australia), Brigham and Women’s Hospital, Harvard Medical School (USA), Institut de Biotecnologia i de Biomedicina (IBB) at the Autonomous University of Barcelona (UAB), Hospital Germans Trias i Pujol, La Jolla Institute for Allergy & Immunology (LIAI) (USA), Keck Medical Center of USC in Los Angeles (USA) and University of Ghent (Belgium).