Barbara K. Felber, Sergio Finkielsztein, George N. Pavlakis, and John N. Vournakis
- The Government, Department of Health and Human Services, Bethesda, MD, US
- Novartis AG, Basel, CH
Cyclical administration regimens of complexes comprising interleukin-15 (“IL-15”) covalently or noncovalently bound to IL-15 receptor alpha (“IL-15Ra”) to patients enhances IL-15-mediated immune function. Cyclical administration regimens achieve plasma levels of IL-15 above basal levels while minimizing the toxicity associated with IL-15 administration. Cyclical administration regimens are useful in the prevention, treatment, and/or management of cancer, infectious diseases, immunodeficienices and lymphopenia. The cyclical administration regimens can use purified soluble forms of IL-15Ra, cells that recombinantly express soluble forms of IL-15Ra, and compositions comprising complexes of IL-15 covalently or non-covalently bound to soluble forms of IL-15Ra, for propagating, activating and/or differentiating IL-15 responsive cells. The IL-15 responsive cells that are immune cells can be administered to prevent, treat and/or manage various disorders, including cancer, infectious disease, immunodeficiency and lymphopenia.
CovalX Technology Used
To determine the molecular mass of HPLC purified and naturally cleaved sIL15Rα, a mass spectrometer that had been modified with a CovalX HM1 detection system was used. Prior to analysis, the samples were mixed with a sinapic acid matrix. Through the use of MALDI-TOF mass spectrometry, researchers were able to compare the mass of a glycosylated form of IL-15Rα with that of the non-glycosylated form to determine the exact percent of the mass that glycosylation accounts for in IL-15Rα.
US 2019/0209653 A1