Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Lion Biotechnologies, Woodland Hills, CA 91367, USA.
Cytokine Growth Factor Rev. 2014 Aug;25(4):377-90. doi: 10.1016/j.cytogfr.2014.07.018. Epub 2014 Aug 1.
The use of cytokines from the IL-2 family (also called the common γ chain cytokine family) such as interleukin (IL)-2, IL-7, IL-15, and IL-21 to activate the immune system of cancer patients is one of the most important areas of current cancer immunotherapy research. The infusion of IL-2 at low or high doses for multiple cycles in patients with metastatic melanoma and renal cell carcinoma was the first successful immunotherapy for cancer proving that the immune system could completely eradicate tumor cells under certain conditions. The initial clinical success observed in some IL-2-treated patients encouraged further efforts focused on developing and improving the application of other IL-2 family cytokines (IL-4, IL-7, IL-9, IL-15, and IL-21) that have unique biological effects playing important roles in the development, proliferation, and function of specific subsets of lymphocytes at different stages of differentiation with some overlapping effects with IL-2. IL-7, IL-15, and IL-21, as well as mutant forms or variants of IL-2, are now also being actively pursued in the clinic with some measured early successes. In this review, we summarize the current knowledge on the biology of the IL-2 cytokine family focusing on IL-2, IL-15 and IL-21. We discuss the similarities and differences between the signaling pathways mediated by these cytokines and their immunomodulatory effects on different subsets of immune cells. Current clinical application of IL-2, IL-15 and IL-21 either as single agents or in combination with other biological agents and the limitation and potential drawbacks of these cytokines for cancer immunotherapy are also described. Lastly, we discuss the future direction of research on these cytokines, such as the development of new cytokine mutants and variants for improving cytokine-based immunotherapy through differential binding to specific receptor subunits.
使用白细胞介素（IL）-2、IL-7、IL-15 和 IL-21 等来自 IL-2 家族（也称为共同γ链细胞因子家族）的细胞因子激活癌症患者的免疫系统是当前癌症免疫治疗研究的最重要领域之一。在转移性黑色素瘤和肾细胞癌患者中多次输注低剂量或高剂量的 IL-2 是第一种成功的癌症免疫疗法，证明在某些条件下免疫系统可以完全消灭肿瘤细胞。在一些接受 IL-2 治疗的患者中观察到的初步临床成功鼓励进一步努力，重点开发和改进其他 IL-2 家族细胞因子（IL-4、IL-7、IL-9、IL-15 和 IL-21）的应用，这些细胞因子具有独特的生物学效应，在不同分化阶段的特定淋巴细胞亚群的发育、增殖和功能中发挥重要作用，与 IL-2 有一些重叠效应。IL-7、IL-15 和 IL-21 以及 IL-2 的突变体或变体也正在临床上积极探索，取得了一些早期的成果。在这篇综述中，我们总结了目前关于 IL-2 细胞因子家族生物学的知识，重点介绍了 IL-2、IL-15 和 IL-21。我们讨论了这些细胞因子介导的信号通路的异同及其对不同免疫细胞亚群的免疫调节作用。目前 IL-2、IL-15 和 IL-21 的临床应用，无论是作为单一药物还是与其他生物制剂联合应用，以及这些细胞因子在癌症免疫治疗中的局限性和潜在缺点也进行了描述。最后，我们讨论了这些细胞因子的未来研究方向，例如通过与特定受体亚基的差异结合开发新的细胞因子突变体和变体来改善基于细胞因子的免疫疗法。
