IL-15R Alpha Forms, Cells Expressing IL-15R Alpha Forms, And Therapeutic Uses of IL-15R Alpha and IL-15/IL-15R Alpha Complexes

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Inventors

Barbara K. Felber, Sergio Finkielsztein, George N. Pavlakis, and John N. Vournakis

Assignees

  1. The Government, Department of Health and Human Services, Bethesda, MD, US
  2. Novartis AG, Basel, CH

Abstract

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

HM1

Outcomes

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.

Patent Number

US 2019/0209653 A1

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Categories : Patents, HM5