Non-immunosuppressive FTY720-derivative OSU-2S mediates reactive oxygen species-mediated cytotoxicity in canine B-cell lymphoma.
Mani R, Yan R, Mo X, Chen CS, Phelps MA, Klisovic R, Byrd JC, Kisseberth WC, London CA, Muthusamy N
Vet Comp Oncol in press 05/02/2016
OSU-2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti-tumour activity in several haematological and solid tumour models. We have recently shown OSU-2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre-clinical activity of OSU-2S in spontaneous B-cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU-2S mediated apoptosis in canine B-cell lines and primary B-cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU-2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU-2S-mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU-2S as small molecule for treating people and dogs with lymphoma.Full Text