Abstract

In one aspect, described herein are cyclical administration regimens for the administration of complexes comprising interleukin-15 ("IL-15") covalently or noncovalently bound to IL-15 receptor alpha ("IL-15Ra") to patients in order to enhance IL-15 -mediated immune function. In one aspect, these cyclical administration regimens achieve plasma levels of IL-15 above basal levels while minimizing the toxicity associated with IL-15 administration. In a specific aspect, the cyclical administration regimens are useful in the prevention, treatment, and/or management of disorders in which enhancing IL- 15-mediated function is beneficial, such as cancer, infectious diseases, immunodeficienices and lymphopenia. Also described herein are 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. Further described herein are host cells that recombinantly express IL15-Ra derivatives comprising a mutation or deletion in the extracellular domain cleavage site, including IL-15Ra derivatives comprising the extracellular domain of IL-15Ra and a transmembrane domain of a heterologous molecule. In addition, described herein are methods for propagating, activating and/or differentiating IL-15 responsive cells, comprising co-culturing an IL-15 responsive cell(s) with a host cell(s) that recombinantly expresses IL-15Ra, and isolating the IL-15 responsive cell(s) from the host cell(s). The IL-15 responsive cells that are immune cells can be administered to prevent, treat and/or manage various disorders, including cancer, an infectious disease, an immunodeficiency and lymphopenia. Further, described herein are methods of enhancing IL-15 -mediated immune function as well as methods for preventing, treating and/or managing disorders in which enhancing IL- 15- mediated function is beneficial, such as cancer, in a subject, the methods comprising administering to the subject a host cell that recombinantly expresses an IL-15Ra described herein.


Claims

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