Fc γ receptor compositional heterogeneity: Considerations for immunotherapy development.
Fc γ receptor compositional heterogeneity: Considerations for immunotherapy development.
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DOI：
10.1074/jbc.rev120.013168
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Barb AW
中科院分区：
文献类型：
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作者：
Barb AW
抗体结合可结晶片段（Fc）γ受体（Fcγ R）由白细胞表达，一旦与抗体包被的靶标结合，就会激活或抑制细胞应答。需要FcγR结合以获得治疗效果的治疗性mAb现在是多种疾病的一线治疗。然而，尽管Fcγ R占抗体-受体复合物的一半，但关注Fcγ R的开发工作却少得多。最近基于工程细胞的免疫疗法的成功现在提供了将修饰的Fcγ R引入临床的机制。Fcγ R具有高度异质性，因为许多基因具有多个功能不同的等位基因，存在膜栓系和可溶性形式，以及高度的翻译后修饰，特别是天冬酰胺连接聚糖。限制FcγR改善的一个重要因素是对人体中存在的内源性受体形式缺乏基本了解。本文综述了从原代人白细胞中分离的Fcγ R的组成，总结了最近对Fcγ R进行工程改造的努力，并总结了潜在的FcγR功能，以丰富增强功能的描述。对FcγR生物学的进一步了解将有助于开发针对免疫相关疾病的新的临床治疗方法。
The antibody-binding crystallizable fragment (Fc) γ receptors (FcγRs) are expressed by leukocytes and activate or suppress a cellular response once engaged with an antibody-coated target. Therapeutic mAbs that require FcγR binding for therapeutic efficacy are now frontline treatments for multiple diseases. However, substantially fewer development efforts are focused on the FcγRs, despite accounting for half of the antibody–receptor complex. The recent success of engineered cell-based immunotherapies now provides a mechanism to introduce modified FcγRs into the clinic. FcγRs are highly heterogeneous because of multiple functionally distinct alleles for many genes, the presence of membrane-tethered and soluble forms, and a high degree of post-translational modification, notably asparagine-linked glycans. One significant factor limiting FcγR improvement is the fundamental lack of knowledge regarding endogenous receptor forms present in the human body. This review describes the composition of FcγRs isolated from primary human leukocytes, summarizes recent efforts to engineer FcγRs, and concludes with a description of potential FcγR features to enrich for enhanced function. Further understanding FcγR biology could accelerate the development of new clinical therapies targeting immune-related disease.