3.8 Review

IgE Antibodies: From Structure to Function and Clinical Translation

期刊

ANTIBODIES
卷 8, 期 1, 页码 -

出版社

MDPI
DOI: 10.3390/antib8010019

关键词

Immunoglobulin E; Fc epsilon RI; CD23; allostery; cancer immunotherapy; AllergoOncology; IgE effector functions; monocytes; macrophages; ADCC

资金

  1. Medical Research Council UK [G0501494, G1100090, MR/L023091/1]
  2. Wellcome Trust [076343]
  3. Asthma UK [AUK-IG-2016-338]
  4. Breast Cancer Now [147]
  5. Cancer Research UK [C30122/A11527, C30122/A15774]
  6. CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre [C10355/A15587]
  7. National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London [IS-BRC-1215-20006]
  8. MRC [MR/L023091/1, G1100090, G0200486, G0501494] Funding Source: UKRI

向作者/读者索取更多资源

Immunoglobulin E (IgE) antibodies are well known for their role in mediating allergic reactions, and their powerful effector functions activated through binding to Fc receptors Fc epsilon RI and Fc epsilon RII/CD23. Structural studies of IgE-Fc alone, and when bound to these receptors, surprisingly revealed not only an acutely bent Fc conformation, but also subtle allosteric communication between the two distant receptor-binding sites. The ability of IgE-Fc to undergo more extreme conformational changes emerged from structures of complexes with anti-IgE antibodies, including omalizumab, in clinical use for allergic disease; flexibility is clearly critical for IgE function, but may also be exploited by allosteric interference to inhibit IgE activity for therapeutic benefit. In contrast, the power of IgE may be harnessed to target cancer. Efforts to improve the effector functions of therapeutic antibodies for cancer have almost exclusively focussed on IgG1 and IgG4 subclasses, but IgE offers an extremely high affinity for Fc epsilon RI receptors on immune effector cells known to infiltrate solid tumours. Furthermore, while tumour-resident inhibitory Fc receptors can modulate the effector functions of IgG antibodies, no inhibitory IgE Fc receptors are known to exist. The development of tumour antigen-specific IgE antibodies may therefore provide an improved immune functional profile and enhanced anti-cancer efficacy. We describe proof-of-concept studies of IgE immunotherapies against solid tumours, including a range of in vitro and in vivo evaluations of efficacy and mechanisms of action, as well as ex vivo and in vivo safety studies. The first anti-cancer IgE antibody, MOv18, the clinical translation of which we discuss herein, has now reached clinical testing, offering great potential to direct this novel therapeutic modality against many other tumour-specific antigens. This review highlights how our understanding of IgE structure and function underpins these exciting clinical developments.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

3.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据