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The immune stimulatory cytokine interleukin-15 was recognized as one of the most promising cancer cure drug in a NIH guided review and is currently in clinical trial alone or as an adjuvant for certain types of metastatic solid tumors. IL-15 is an essential survival factor for natural killer (NK), natural killer-like T (NKT), and CD44hi memory CD8 T cells. The bioactivity of IL-15 in vivo is conferred mainly through a trans-presentation mechanism in which IL-15 is presented in complex with the α-subunit of soluble IL-15 receptor (IL-15R) to NK, NKT or T cells rather than directly interacts with membrane-bound IL-15R. With these understandings, recent studies have been focused on generating IL-15 agonists which consist of IL-15 and partial or whole of soluble IL-15R to improve its in vivo bioactivity.
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