Karyopharm Therapeutics Inc.
IL-12 COMPOSITIONS AND METHODS OF USE IN HEMATOPOIETIC RECOVERY

Abstract:

Aspects and embodiments of the instant disclosure provide therapeutic methods and compositions comprising interleukin 12 (IL-12) useful for improving hematopoietic recovery HSCT transplantation in a subject. In particular, the instant disclosure provide exemplary methods and compositions comprising IL-12 promoted hematopoiesis and increased the recovery of peripheral blood cells and survival in lethally irradiated mice as effectively as a BMCT, indicating that rHuIL-12 therapy can to increase HSC engraftment following HSCT. We identified IL-12R.beta.2 expressing cells in irradiated mouse bone marrow which are potential targets of IL-12. Administration of rMuIL-12 increased the number of IL-12R.quadrature.2 expressing Lin- cells in mouse bone marrow, indicating that bone marrow HSCs and niche cells are the direct target of rMuIL-12 and that hematopoiesis-promoting activity of rMuIL-12 is mediated by IL-12 receptors on HSCs. Finally, we show expression of IL-12.beta.2 on human bone marrow lin- and CD34+ cells, indicating a potential role for IL-12 in human transplantation.