IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation.
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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DOI：
10.1016/j.pharmthera.2016.10.012
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发表时间：
2017-02
影响因子：
13.5
通讯作者：
J. Van den Bergh;E. Lion;V. V. Van Tendeloo-V.;E. Smits
中科院分区：
文献类型：
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作者：
J. Van den Bergh;E. Lion;V. V. Van Tendeloo-V.;E. Smits
白细胞介素(IL)-15作为一种单独的治疗方法，可以激活免疫效应细胞的抗肿瘤功能，导致肿瘤明显消退。有趣的是，将IL-15与其受体（IL-15Rα）的α-片段结合，也称为IL-15表达，增加了IL-15的体内半衰期，并增强了IL-15与表达IL-15Rβγ的细胞（如NK细胞和CD8+T细胞）的结合。这些特征扩大了IL-15的信号传递，从而提高了NK细胞和CD8+T细胞的增殖和抗肿瘤活性，最终增强了对肿瘤细胞的杀伤作用。在这篇综述中，我们讨论了目前正在进行临床前研究的IL-15表达机制的抗肿瘤策略。此外，我们还概述了IL-15/IL-15Rα复合物与其他抗肿瘤疗法联合的研究。这些有希望的临床前研究结果激发了一些临床试验，以测试IL-15表达策略治疗血液病和晚期实体瘤的安全性和有效性。
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.