Preijers F W, Tax W J, De Witte T, Janssen A, vd Heijden H, Vidal H, Wessels J M, Capel P J
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Br J Haematol. 1988 Nov;70(3):289-94. doi: 10.1111/j.1365-2141.1988.tb02484.x.
Immunotoxins (ITs) appear to vary considerably in their killing efficiency towards antigen positive cells. In order to unravel the mechanisms underlying these differences, the parameters responsible for these variations were studied. The efficacy of the monoclonal antibodies (MoAbs) WT32 (CD3), OKT4 (CD4), T101 (CD5), WT1 (CD7) and WT82 (CD8) conjugated to ricin A-chain was expressed by the extent of protein synthesis inhibition of four leukaemic T cell lines (CEM, GH1, Jurkat and HPB-ALL). Large differences in cytotoxicity were observed. Efficient inhibition of protein synthesis was seen with anti-CD3 IT, anti-CD5 IT and anti-CD7 IT. In these cases the cytotoxicity was related to the antigen density on the target cell membrane. Anti-CD4 IT inhibited poorly and anti-CD8 IT was ineffective, even on cell lines with a high expression of the corresponding antigen. When antigen density and cytotoxicity were plotted for all CD antigens, no correlation could be found. Subsequently, internalization was studied with 125Iodine-labelled antibodies. Anti-CD7 showed the fastest internalization rate, followed by anti-CD3 and anti-CD5. Anti-CD4 and anti-CD8 antibodies were respectively moderately and hardly internalized. When the absolute amount of internalized MoAb was calculated, a highly significant correlation with cytotoxicity was found. We conclude that the degree of antigen expression is not so important as the absolute amount of antibody internalized in predicting the efficacy of ITs.
免疫毒素（ITs）对抗原阳性细胞的杀伤效率似乎有很大差异。为了阐明这些差异背后的机制，对导致这些差异的参数进行了研究。与蓖麻毒素A链偶联的单克隆抗体（MoAbs）WT32（CD3）、OKT4（CD4）、T101（CD5）、WT1（CD7）和WT82（CD8）的效力通过对四种白血病T细胞系（CEM、GH1、Jurkat和HPB - ALL）蛋白质合成抑制的程度来表示。观察到细胞毒性存在很大差异。抗CD3免疫毒素、抗CD5免疫毒素和抗CD7免疫毒素能有效抑制蛋白质合成。在这些情况下，细胞毒性与靶细胞膜上的抗原密度有关。抗CD4免疫毒素抑制作用较差，抗CD8免疫毒素即使对相应抗原高表达的细胞系也无效。当绘制所有CD抗原的抗原密度和细胞毒性关系图时，未发现相关性。随后，用125碘标记的抗体研究内化情况。抗CD7显示出最快的内化速率，其次是抗CD3和抗CD5。抗CD4和抗CD8抗体分别是中等程度内化和几乎不内化。当计算内化单克隆抗体的绝对量时，发现其与细胞毒性高度相关。我们得出结论，在预测免疫毒素的效力时，抗原表达程度不如内化抗体的绝对量重要。
