文章：

癌症中的Fcγ受体和免疫调节抗体

Fcγ receptors and immunomodulatory antibodies in cancer

原文发布日期：2023-12-07

DOI: 10.1038/s41568-023-00637-8

类型: Review Article

开放获取: 否

英文摘要：

The discovery of both cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) as negative regulators of antitumour immunity led to the development of numerous immunomodulatory antibodies as cancer treatments. Preclinical studies have demonstrated that the efficacy of immunoglobulin G (IgG)-based therapies depends not only on their ability to block or engage their targets but also on the antibody’s constant region (Fc) and its interactions with Fcγ receptors (FcγRs). Fc–FcγR interactions are essential for the activity of tumour-targeting antibodies, such as rituximab, trastuzumab and cetuximab, where the killing of tumour cells occurs at least in part due to these mechanisms. However, our understanding of these interactions in the context of immunomodulatory antibodies designed to boost antitumour immunity remains less explored. In this Review, we discuss our current understanding of the contribution of FcγRs to the in vivo activity of immunomodulatory antibodies and the challenges of translating results from preclinical models into the clinic. In addition, we review the impact of genetic variability of human FcγRs on the activity of therapeutic antibodies and how antibody engineering is being utilized to develop the next generation of cancer immunotherapies.

摘要翻译： 

细胞毒性T淋巴细胞相关抗原4（CTLA4）与程序性细胞死亡蛋白1（PD1）作为抗肿瘤免疫负向调控因子的发现，催生了众多免疫调节抗体作为癌症疗法的发展。临床前研究表明，基于免疫球蛋白G（IgG）的疗法不仅依赖于其阻断或结合靶标的能力，更与抗体恒定区（Fc）及其与Fcγ受体（FcγR）的相互作用密切相关。Fc–FcγR相互作用对于利妥昔单抗、曲妥珠单抗和西妥昔单抗等靶向肿瘤抗体至关重要，这些抗体杀伤肿瘤细胞的机制至少部分源于此类相互作用。然而，对于旨在增强抗肿瘤免疫的免疫调节抗体中这些相互作用的理解仍待深入。本文综述当前对FcγR在免疫调节抗体体内活性中作用的认识，探讨临床前模型向临床转化面临的挑战，同时阐述人FcγR遗传变异对治疗性抗体活性的影响，以及如何通过抗体工程技术开发新一代癌症免疫疗法。

原文链接：

Fcγ receptors and immunomodulatory antibodies in cancer