Nokta M, Tolpin M D, Nadler P I, Pollard R B
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Antiviral Res. 1994 May;24(1):17-26. doi: 10.1016/0166-3542(94)90048-5.
Human CMV causes a number of diseases that cause considerable morbidity and that can be life-threatening in immunocompromised patients, particularly those with AIDS. Ganciclovir (GCV) and Foscarnet (PFA) are currently the drugs of choice for management of CMV disease. Both are not without side effects and have a relatively narrow margin of safety. In this report the effects of a human IgG1 neutralizing monoclonal antibody MSL-109 (MSL, Sandoz Pharmaceuticals) on CMV replication was examined both alone or in combination with either GCV or PFA. Human embryonic lung fibroblasts were infected with CMV strain AD169 with a multiplicity of infection of 3 plaque forming units/cell for 1 h. Prior to infection the virus was incubated for 30 min at 37 degrees C with serial concentrations of the MSL Ab (0.1-3.0 micrograms/ml). Concentrations of GCV (0.3 to 30 microM) or PFA (50-400 microM) were added to CMV-infected cells that had been either previously incubated with MSL or not. Four days after infection CMV replication was measured by DNA/DNA probe hybridization using the Hybriwix system. MSL in combination with GCV had an additive effect that was observed at concentrations of GCV of 3-10 microM and MSL of 1-10 micrograms/ml. On the other hand, MSL (3-10 micrograms/ml) together with PFA (100-400 microM) produced a synergistic effect on CMV replication. The data suggest that MSL at doses achievable in humans, enhanced GCV- and PFA-induced antiviral effect in a dose-dependent manner and that the combination might be clinically useful in the treatment of CMV disease.
人巨细胞病毒（Human CMV）可引发多种疾病，这些疾病会导致相当高的发病率，并且在免疫功能低下的患者中，尤其是艾滋病患者中，可能会危及生命。更昔洛韦（GCV）和膦甲酸钠（PFA）是目前治疗巨细胞病毒疾病的首选药物。这两种药物都有副作用，且安全范围相对较窄。在本报告中，研究了人IgG1中和单克隆抗体MSL - 109（MSL，山德士制药公司）单独使用或与GCV或PFA联合使用时对巨细胞病毒复制的影响。用人巨细胞病毒AD169株以感染复数为3个空斑形成单位/细胞感染人胚肺成纤维细胞1小时。在感染前，将病毒与系列浓度的MSL抗体（0.1 - 3.0微克/毫升）在37℃孵育30分钟。将GCV（0.3至30微摩尔）或PFA（50 - 400微摩尔）的浓度添加到先前已与MSL孵育或未孵育的巨细胞病毒感染细胞中。感染后四天，使用Hybriwix系统通过DNA/DNA探针杂交测量巨细胞病毒复制。MSL与GCV联合使用时具有相加作用，在GCV浓度为3 - 10微摩尔和MSL浓度为1 - 10微克/毫升时可观察到。另一方面，MSL（3 - 10微克/毫升）与PFA（100 - 400微摩尔）一起对巨细胞病毒复制产生协同作用。数据表明，在人体可达到的剂量下，MSL以剂量依赖方式增强了GCV和PFA诱导的抗病毒作用，并且这种联合用药在治疗巨细胞病毒疾病方面可能具有临床应用价值。
