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WALTHAM, MA, United States

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.95K | Year: 2014

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

Nkt Therapeutics, Inc. | Entity website

Jenny Gumperz, Ph.D ...

Nkt Therapeutics, Inc. | Date: 2015-07-28

Pharmaceutical compositions and treatments involving iNKT cell activation are provided.

Nkt Therapeutics, Inc. | Date: 2012-10-26

Methods of treatment to suppress an immune response are provided. The method comprises administering to a subject in need of treatment a naked blocking antibody that binds selectively iNKT cells in an amount effective to suppress the subjects iNKT cell function. Compositions comprising, an isolated, humanized antibody that binds selectively iNKT cells are also provided.

Waters E.K.,Cambridge Healthcare | Waters E.K.,Archemix | Genga R.M.,Cambridge Healthcare | Genga R.M.,Archemix | And 9 more authors.
Journal of Thrombosis and Haemostasis | Year: 2013

Background: Tissue factor pathway inhibitor (TFPI) is a multidomain protein that negatively regulates the coagulation cascade. TFPI inhibits the tissue factor (TF)-activated factor VII-activated FX (FXa) complex during TF-mediated coagulation initiation. The aptamer BAX 499 binds specifically to TFPI and inhibits its function, mediating a procoagulant effect in both in vitro and in vivo models of hemophilia. Objectives: This study sought to identify the regions of TFPI that are critical for BAX 499 binding, and to determine how binding mediates aptamer inhibition of TFPI. Methods and Results: In vitro biochemical methods were used to evaluate the BAX 499 interaction with and inhibition of TFPI. Binding experiments indicated that the full-length TFPI protein is required for tight aptamer binding. Binding-competition experiments implicated the Kunitz 1, Kunitz 3 and C-terminal domains of TFPI in aptamer binding, a finding that is supported by hydrogen-deuterium exchange experiments, and indicated that aptamer and FXa can bind simultaneously to TFPI. In enzymatic assays, BAX 499 inhibited TFPI in a manner that is distinct from domain-specific antibodies, and aptamer inhibitory activity is reduced in the presence of the TFPI cofactor protein S. Conclusions: These studies demonstrate that BAX 499 binds to TFPI via multiple domains of the protein in a manner that is distinct from other TFPI inhibitors, mediating a mechanism of inhibition that does not involve direct competition with FXa. With this unique inhibitory mechanism, BAX 499 provides a useful tool for studying TFPI biology in health and disease. © 2013 International Society on Thrombosis and Haemostasis.

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