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Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases

机译:Fc受体及其对治疗性抗体治疗病毒性疾病功效的影响

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摘要

The lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. In recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, Ebola virus and Hendra virus. The binding affinity of these antibodies can directly impact their therapeutic efficacy. However, we and others have also demonstrated that the subtype of Fc-gamma receptors (FcγRs) engaged influences the stoichiometric requirement for virus neutralization. Hence, the development of therapeutic antibodies against infectious diseases should consider the FcγRs engaged and Fc-effector functions involved. This review highlights the current state of knowledge about FcγRs and FcγR effector functions involved in virus neutralization, with emphasis on factors that can affect FcγR engagement. A better understanding of Fc-FcγR interactions during virus neutralization will allow development of therapeutic antibodies that are efficacious and can be administered with minimal side effects.
机译:由于缺乏针对几种重要病毒性疾病的疫苗,因此必须开发能够挽救生命和控制流行病的疗法。近年来,由于治疗性抗体具有良好的安全性和抗病毒性,如抗呼吸道合胞病毒,埃博拉病毒和亨德拉病毒,在临床上取得了成功,因此引起了广泛关注。这些抗体的结合亲和力可直接影响其治疗功效。但是,我们和其他人也已经证明,参与的Fc-γ受体(FcγRs)的亚型会影响病毒中和的化学计量要求。因此,针对传染病的治疗性抗体的开发应考虑参与的FcγR和涉及的Fc效应子功能。这篇综述重点介绍了与病毒中和有关的FcγR和FcγR效应子功能的当前知识状态,着重介绍了可能影响FcγR参与的因素。病毒中和过程中对Fc-FcγR相互作用的更好理解将允许开发有效的治疗性抗体,并且可以以最小的副作用进行给药。

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