Letvin N L, Ritz J, Guida L J, Yetz J M, Lambert J M, Reinherz E L, Schlossman S F
Blood. 1985 Oct;66(4):961-6.
The effects of in vivo administration of three monoclonal antibodies specific for T11, the E rosette receptor on T lymphocytes, were examined in the rhesus monkey (Macaca mulatta). These three monoclonal antibodies were of different isotypes and were shown in in vitro studies to have differing affinities for the monkey T11 structure. Furthermore, each antibody induced antigenic modulation of T11 from the cell membrane of the lymphocytes to varying degrees in vitro. In vivo infusion of each of these antibodies into normal rhesus monkeys caused remarkably different effects on the circulating T lymphocyte pool. Infusion of these antibodies at doses of 2 mg/kg caused the coating of circulating T lymphocytes with antibody, the modulation of T11 off the T cell surface and the transient clearance of T cells from the circulation. Yet, the variation in the extent to which these effects were seen with these different antibodies indicates that extrapolating from studies of the in vivo use of one antibody to the use of another may be quite difficult. These studies clearly indicate the strengths of this nonhuman primate system for exploring the uses of monoclonal antilymphocyte antibodies as therapeutic agents. They, however, also demonstrate that differences may exist in the affinity of a particular antibody for homologous lymphocyte surface structures in humans and in a nonhuman primate species. These differences may make it difficult to predict the precise effects that the infusion of an antibody will cause in humans on the basis of alterations it induces in nonhuman primates.
在恒河猴(猕猴属)中研究了体内给予三种针对T11(T淋巴细胞上的E玫瑰花结受体)的单克隆抗体的效果。这三种单克隆抗体属于不同的同种型,并且在体外研究中显示对猴T11结构具有不同的亲和力。此外,每种抗体在体外均能不同程度地诱导T11从淋巴细胞细胞膜上发生抗原调变。将这些抗体分别体内注入正常恒河猴后,对循环中的T淋巴细胞库产生了显著不同的影响。以2mg/kg的剂量注入这些抗体导致循环中的T淋巴细胞被抗体包被,T11从T细胞表面调变,以及T细胞从循环中短暂清除。然而,这些不同抗体产生这些效应的程度存在差异,这表明从一种抗体的体内使用研究推断另一种抗体的使用情况可能相当困难。这些研究清楚地表明了这种非人灵长类动物系统在探索单克隆抗淋巴细胞抗体作为治疗剂用途方面的优势。然而,它们也证明了特定抗体对人类和非人灵长类动物物种中同源淋巴细胞表面结构的亲和力可能存在差异。这些差异可能使得难以根据抗体在非人灵长类动物中诱导的变化来预测其注入人体后将产生的精确效应。