Chan Kuan Rong, Ong Eugenia Z, Mok Darren Z L, Ooi Eng Eong
a 1 Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
b 2 Experimental Therapeutics Centre, Agency for Science Technology and Research, 31 Biopolis Way, Singapore 138669, Singapore.
Expert Rev Anti Infect Ther. 2015;13(11):1351-60. doi: 10.1586/14787210.2015.1079127. Epub 2015 Aug 24.
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.
由于缺乏针对几种重要病毒性疾病的疫苗，因此有必要开发治疗方法以挽救生命并控制疫情。近年来，治疗性抗体因其良好的安全性以及在对抗呼吸道合胞病毒、埃博拉病毒和亨德拉病毒等病毒时取得的临床成功而备受关注。这些抗体的结合亲和力会直接影响其治疗效果。然而，我们和其他研究人员也证明，与之结合的Fc-γ受体（FcγRs）亚型会影响病毒中和的化学计量要求。因此，开发针对传染病的治疗性抗体时应考虑所涉及的FcγRs和Fc效应功能。本综述重点介绍了目前关于参与病毒中和的FcγRs和FcγR效应功能的知识现状，重点关注可能影响FcγR结合的因素。更好地了解病毒中和过程中的Fc-FcγR相互作用将有助于开发出有效且副作用最小的治疗性抗体。
