IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation

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• 作者：Johan MJ Van den Bergh^a ; ^{johan.vandenbergh@uantwerpen.be} ; Eva Lion^a ; ^b ; Viggo FI Van Tendeloo^a ; Evelien LJM Smits^a ; ^b ; ^c
• 关键词：ALT-803 ; IL-15 mutant (whereby the amino acid asparagine at position 72 is substituted by an aspartic acid)  ; +  ; sushi domain IL-15Rα (Fig. 1) ; IL ; interleukin ; IL-15Rα ; interleukin-15 receptor alpha ; NK cells ; natural killer cells ; RLI ; IL-15 coupled with a linker to the soluble IL-15Rα sushi domain (Fig. 1)
• 刊名：Pharmacology & Therapeutics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：170
• 期：Complete
• 页码：73-79
• 全文大小：423 K
• 卷排序：170

文摘

Interleukin (IL)-15 as a stand-alone therapy can activate the antitumor functions of immune effector cells resulting in significant tumor regression. Interestingly, combining IL-15 with the α-moiety of its receptor (IL-15Rα), also called IL-15 transpresentation, increases the in vivo half-life of IL-15 and enhances binding of IL-15 with cells expressing the IL-15Rβγ, such as NK cells and CD8+ T cells. These features enlarge the signal transmission of IL-15, resulting in improved proliferation and antitumor activities of both NK cells and CD8+ T cells, eventually leading to enhanced killing of tumor cells. In this review, we discuss the antitumor strategies in which this IL-15 transpresentation mechanism is implemented, that are currently under preclinical investigation. Furthermore, we give an overview of the studies in which the IL-15/IL-15Rα complexes are combined with other antitumor therapies. The promising results in these preclinical studies have incited several clinical trials to test the safety and efficacy of IL-15 transpresentation strategies to treat both hematological and advanced solid tumors.