Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail code L457, Portland, OR, 97239, USA.
Curr Hematol Malig Rep. 2020 Apr;15(2):90-102. doi: 10.1007/s11899-020-00557-6.
CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection.
Letermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kinase, is currently in two phase 3 treatment studies. Adoptive immunotherapy using third-party T cells has proven safe and effective in preliminary studies. Vaccine development continues, with several promising candidates currently under study. No longer limited to DNA polymerase inhibitors, the prevention and treatment of CMV infections in the HCT recipient is a rapidly evolving field which should translate into improvements in CMV-related outcomes.
更昔洛韦和膦甲酸等 CMV DNA 聚合酶抑制剂显著降低了 HCT 受者 CMV 感染的负担。然而,其应用常受到毒性和耐药性的限制。急需具有新颖机制和良好毒性特征的药物。我们综述了 CMV 抗病毒药物和免疫方法在减轻 CMV 感染方面的最新进展。
CMV 末端酶复合物抑制剂来特莫韦于 2017 年获批用于成人 CMV 阳性的异基因 HCT 受者的 CMV 一级预防。CMV UL97 激酶抑制剂马拉韦罗目前正在两项 3 期治疗研究中。使用第三方 T 细胞的过继免疫疗法在初步研究中已被证明是安全有效的。疫苗的开发仍在继续,目前有几个有前途的候选者正在研究中。CMV 感染的预防和治疗不再仅限于 DNA 聚合酶抑制剂,这一领域正在迅速发展,应该会改善与 CMV 相关的结果。