Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Viruses. 2024 May 29;16(6):869. doi: 10.3390/v16060869.
Human cytomegalovirus is a ubiquitous herpesvirus that, while latent in most individuals, poses a great risk to immunocompromised patients. In contrast to directly acting traditional antiviral drugs, such as ganciclovir, we aim to emulate a physiological infection control using T cells. For this, we constructed several bispecific T-cell engager (BiTE) constructs targeting different viral glycoproteins of the murine cytomegalovirus and evaluated them in vitro for their efficacy. To isolate the target specific effect without viral immune evasion, we established stable reporter cell lines expressing the viral target glycoprotein B, and the glycoprotein complexes gN-gM and gH-gL, as well as nano-luciferase (nLuc). First, we evaluated binding capacities using flow cytometry and established killing assays, measuring nLuc-release upon cell lysis. All BiTE constructs proved to be functional mediators for T-cell recruitment and will allow a proof of concept for this treatment option. This might pave the way for strikingly safer immunosuppression in vulnerable patient groups.
人巨细胞病毒是一种普遍存在的疱疹病毒，虽然在大多数人中处于潜伏状态，但对免疫功能低下的患者构成巨大风险。与直接作用的传统抗病毒药物（如更昔洛韦）不同，我们旨在使用 T 细胞模拟生理性感染控制。为此，我们构建了几种针对鼠巨细胞病毒不同病毒糖蛋白的双特异性 T 细胞衔接器（BiTE）构建体，并在体外评估了它们的功效。为了在没有病毒免疫逃逸的情况下分离靶向特异性效应，我们建立了稳定表达病毒靶糖蛋白 B 以及糖蛋白复合物 gN-gM 和 gH-gL 的报告细胞系，以及纳米荧光素酶（nLuc）。首先，我们使用流式细胞术评估了结合能力，并建立了杀伤测定法，测量细胞裂解时 nLuc 的释放。所有 BiTE 构建体都被证明是 T 细胞募集的有效介质，并将为这种治疗选择提供概念验证。这可能为脆弱患者群体中的免疫抑制提供更安全的途径。
