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Il-15r alpha forms, cells expressing il-15r alpha forms, and therapeutic uses of il-15r alpha and il-15/il-15r alpha complexes
专利权人:
ADMUNE THERAPEUTICS LLC
发明人:
申请号:
IL23847615
公开号:
IL238476D0
申请日:
2015.04.26
申请国别(地区):
IL
年份:
2015
代理人:
摘要:
In one aspect, described herein are cyclical administration regimens for the administration of complexes comprising interleukin-15 (&ldquoIL-15&rdquo) covalently or noncovalently bound to IL-15 receptor alpha (&ldquoIL-15Ra&rdquo) 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, immunodeficiencies 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 c
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