Insights into cytokine-receptor interactions from cytokine engineering.
Insights into cytokine-receptor interactions from cytokine engineering.
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DOI：
10.1146/annurev-immunol-032713-120211
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发表时间：
2015
影响因子：
29.7
通讯作者：
Garcia KC
中科院分区：
文献类型：
--
作者：
Spangler JB;Moraga I;Mendoza JL;Garcia KC
细胞因子发挥着广泛的免疫调节作用，对人类生物学和疾病至关重要。然而，天然细胞因子的预期免疫治疗效果往往会因毒性或缺乏疗效而减弱，这两种情况都是由于细胞因子受体的多效性和/或非靶细胞的意外激活所致。随着我们对细胞因子-受体相互作用结构原理的理解不断深入，通过蛋白质工程对细胞因子信号进行基于机制的操纵已成为一种越来越可行和有效的方法。修饰的细胞因子，无论是激动剂还是拮抗剂，都被设计成具有更窄的靶细胞特异性，它们也产生了对细胞因子生物学和信号转导的重要机制见解。在这里，我们回顾了细胞因子工程的理论和实践，并从结构的角度对几种工程细胞因子的机制进行了合理化。我们讨论了基于结构的细胞因子工程如何为细胞因子作为药物打开了新的机会的具体例子，重点是免疫治疗细胞因子干扰素、白介素2和白介素4。
Cytokines exert a vast array of immunoregulatory actions critical to human biology and disease. However, the desired immunotherapeutic effects of native cytokines are often mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cells. As our understanding of the structural principles of cytokine–receptor interactions has advanced, mechanism-based manipulation of cytokine signaling through protein engineering has become an increasingly feasible and powerful approach. Modified cytokines, both agonists and antagonists, have been engineered with narrowed target cell specificities, and they have also yielded important mechanistic insights into cytokine biology and signaling. Here we review the theory and practice of cytokine engineering and rationalize the mechanisms of several engineered cytokines in the context of structure. We discuss specific examples of how structure-based cytokine engineering has opened new opportunities for cytokines as drugs, with a focus on the immunotherapeutic cytokines interferon, interleukin-2, and interleukin-4.
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影响因子：
5.6
作者：
Boulanger, MJ;Chow, DC;Garcia, KC
通讯作者：
Garcia, KC
影响因子：
2.8
作者：
Candolfi M;Kroeger KM;Xiong W;Liu C;Puntel M;Yagiz K;Muhammad AG;Mineharu Y;Foulad D;Wibowo M;Assi H;Baker GJ;Lowenstein PR;Castro MG
通讯作者：
Castro MG
DOI：
10.4049/jimmunol.1003961
发表时间：
2011-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castro I;Yu A;Dee MJ;Malek TR
通讯作者：
Malek TR
DOI：
10.1073/pnas.0609001104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Brideau-Andersen, Amy D.;Huang, Xiaojian;Patten, Phillip A.
通讯作者：
Patten, Phillip A.
影响因子：
4.8
作者：
Caput, D;Laurent, P;Ferrara, P
通讯作者：
Ferrara, P