Depletion of iNKT Cells in the Treatment of Hypoxic Crises in Sickle Cell Mice

There is a central role for iNKT cells in mediating inflammatory responses in sickle cell disease. NKT Therapeutics has developed a humanized monoclonal antibody (NKTT120) that can specifically mediate iNKT cell depletion by antibody and complement directed cellular cytotoxicity. We are currently engaged in a safety/PK Phase 1 study in stable sickle cell disease patients. Although the use of specific murine SCD models has helped in defining the role of iNKT cells in SCD, the fact that NKTT120 does not crossreact with murine iNKT cells has limited our ability to assess the short and long term impact of iNKT cell depletion on the pathology of SCD. Our recent identification of a monoclonal antibody (NKT-14) that binds to the mouse NKT cell to mediate murine iNKT cell depletion provides us with a unique opportunity to directly explore the impact of iNKT cell depletion in mediating the pathology of SCD. The antibody is specific for the mouse iTCR and, when bound, promotes a rapid and long lasting (gt 14 days) dep