Coming together at the hinges: Therapeutic prospects of IgG3.
Coming together at the hinges: Therapeutic prospects of IgG3.
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DOI：
10.1080/19420862.2021.1882028
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发表时间：
2021-01
期刊：
影响因子：
5.3
通讯作者：
Ackerman ME
中科院分区：
文献类型：
--
作者：
Chu TH;Patz EF Jr;Ackerman ME
在已批准的单抗疗法和Fc融合蛋白生物制品的格式中，明显缺乏人IgG3亚类。对同种异型的显著变异可能导致的快速降解、血浆半衰期的缩短和免疫原性的提高的担忧显然超过了免疫球蛋白3的潜在优势，包括对激活Fcγ受体的高亲和力，有效的补体结合，以及似乎更适合于低丰度靶的长铰链。本综述旨在强调IgG3的不同特征，并探讨其在免疫应答中的功能作用。我们介绍了自然免疫和重组抗体疗法的研究，阐明了IgG3的关键贡献，并讨论了不再明显相关的历史障碍。总的来说，这一证据激发了对这一独特抗体亚类用于治疗人类疾病的临床进展的深思熟虑的重新考虑。缩写：ADCC-抗体依赖的细胞介导的细胞毒作用ADE-抗体依赖的增强艾滋病激活诱导的胞苷脱氨酶CH-恒重CHF-补体因子hcSR-类开关重组EM-电子显微镜Fab-片段，抗原结合Fc-片段，结晶FcRn-新生儿Fc受体FcγR-Fcγ受体HIV-人类免疫缺陷病毒Ig-免疫球蛋白IgH-免疫球蛋白重链基因NHP-非人类灵长类
The human IgG3 subclass is conspicuously absent among the formats for approved monoclonal antibody therapies and Fc fusion protein biologics. Concern about the potential for rapid degradation, reduced plasma half-life, and increased immunogenicity due to marked variation in allotypes has apparently outweighed the potential advantages of IgG3, which include high affinity for activating Fcγ receptors, effective complement fixation, and a long hinge that appears better suited for low abundance targets. This review aims to highlight distinguishing features of IgG3 and to explore its functional role in the immune response. We present studies of natural immunity and recombinant antibody therapies that elucidate key contributions of IgG3 and discuss historical roadblocks that no longer remain clearly relevant. Collectively, this body of evidence motivates thoughtful reconsideration of the clinical advancement of this distinctive antibody subclass for treatment of human diseases. Abbreviations: ADCC - Antibody-Dependent Cell-mediated CytotoxicityADE – Antibody-dependent enhancementAID – Activation-Induced Cytidine DeaminaseCH – Constant HeavyCHF – Complement factor HCSR – Class Switch RecombinationEM - Electron MicroscopyFab – Fragment, antigen bindingFc – Fragment, crystallizableFcRn – Neonatal Fc ReceptorFcγR – Fc gamma ReceptorHIV – Human Immunodeficiency VirusIg - ImmunoglobulinIgH – Immunoglobulin Heavy chain geneNHP – Non-Human Primate
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影响因子：
7.3
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影响因子：
64.5
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作者：
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影响因子：
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作者：
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通讯作者：
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