Effect of ONO-4053 on Fc Epsilon RI Stimulated-Mast Cell Activation
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Shinsuke Yamaguchi, Yutaka Okada, Yoko Matsunaga, Fumio Nambu
Rationale: As prostaglandin D2 (PGD2), a chemical mediator released in large amounts from mast cells, is known to be involved in a number of allergic responses, blockage of PGD2 action might be beneficial for the treatment of allergic disease.  ONO-4053 is an orally active DP1 (a PGD2 receptor) antagonist in phase 2 clinical trial for the treatment of allergic rhinitis.  The purpose of this study was to investigate the effect of ONO-4053 on mast cell activation after Fc epsilonRI stimulation.

Methods: Human mast cells were differentiated from CD34-positive bone marrow cells in the presence of stem cell factor (SCF), IL-6 and IL-3.  After overnight sensitization with human myeloma IgE, the cells were incubated with and without ONO-4053 at 37 °C for 60 min.  Goat anti-human IgE antibody was then added to initiate the reaction, and the amounts of histamine and PGD2 after 30 min reaction, and cytokines after 6 hours reaction were determined.

Results: ONO-4053 concentration-dependently inhibited Fc epsilonRI-stimulated histamine release and PGD2 production in human mast cells, but did not affect cytokines production in these cells.  Other DP1 antagonists had no effect on histamine release, PGD2 production, or cytokines production in the stimulated mast cells.

Conclusions: The findings of this study indicate that ONO-4053 would be clinically useful for a variety of allergic diseases, including allergic rhinitis, by the action of both DP1 antagonism and suppression of mast cell activation.