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[免疫毒素对人红系肿瘤细胞的选择性细胞毒性作用]

[Selective cytotoxic effect of an immunotoxin on human erythroid tumor cells].

作者信息

Tonevitskiĭ A G, Agapov I I, Mechetner E B

出版信息

Mol Biol (Mosk). 1991 Sep-Oct;25(5):1181-7.

PMID:1753950
Abstract

The possibility of efficient directed elimination of human erythroblastoid cells by the conjugate of IgM-monoclonal antibody HAE9 directed against the erythroblast antigen and the A-chain of a plant toxin ricin has been demonstrated. The conjugate contained 2 molecules of A-chain per one antibody molecule. The efficiencies of the cytotoxic effect of native ricin and the conjugate were compared according to the number of binding sites on the surface of K562 cells as well as to the internalization rate of these molecules. As was shown, that the number of binding sites for the antibody approaches 2.7.10(4) molecules/cell, K a being equal to 1.7.10(8) M-1 while for ricin these indices constitute 2.4.10(5) and 4.6.10(8) M-1. Almost 100% of antibodies and 36% of ricin are internalized within 10 min at 37 degrees C. At a concentration 10(-11) of native ricin and 10(-10) of immunotoxin the 50% inhibition of growth of K562 cells carrying the erythroblast antigen on their surface is observed.

摘要

已证实,针对成红细胞抗原的IgM单克隆抗体HAE9与植物毒素蓖麻毒蛋白A链的缀合物能够有效地直接消除人成红细胞样细胞。该缀合物每个抗体分子含有2个A链分子。根据K562细胞表面结合位点的数量以及这些分子的内化率,比较了天然蓖麻毒蛋白和缀合物的细胞毒性作用效率。结果表明,抗体的结合位点数量接近2.7×10⁴个/细胞,Kₐ等于1.7×10⁸ M⁻¹,而蓖麻毒蛋白的这些指标分别为2.4×10⁵和4.6×10⁸ M⁻¹。在37℃下,几乎100%的抗体和36%的蓖麻毒蛋白在10分钟内被内化。在天然蓖麻毒蛋白浓度为10⁻¹¹和免疫毒素浓度为10⁻¹⁰时,观察到表面携带成红细胞抗原的K562细胞生长受到50%的抑制。

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