Raso V, Griffin T
Cancer Res. 1981 Jun;41(6):2073-8.
Hybrid antibodies possessing one binding site for the toxic lectin ricin and a companion site directed against human immunoglobulin were constructed in vitro. This bifunctional reagent specifically attached to human lymphocyte surface immunoglobulin determinants and, thus situated, could simultaneously capture ricin molecules or its toxic A chain. Attachment of these components to the cell was revealed by specific fluorescein-labeled antibodies. Once concentrated at the target cell membrane, hybrid-bound toxin was subsequently released to function via its normal mechanism of biological action. It gained access to ribosomes, its intracellular target, and curtailed protein synthesis. Toxicity was not augmented for immunoglobulin-negative cells to which hybrid could not bind and free human immunoglobulin G could competitively block the enhanced effects observed for immunoglobulin-bearing cell lines. These results indicate that hybrid antibodies may be utilized to carry active agents within close proximity to the membrane of a specified cell type and thereby selectively enhance their effect.
在体外构建了具有一个针对毒性凝集素蓖麻毒素的结合位点和一个针对人免疫球蛋白的伴随位点的杂合抗体。这种双功能试剂特异性地附着于人淋巴细胞表面免疫球蛋白决定簇，处于这种位置时，它能够同时捕获蓖麻毒素分子或其毒性A链。通过特异性荧光素标记抗体可显示这些成分与细胞的附着情况。一旦在靶细胞膜上聚集，杂合结合的毒素随后通过其正常的生物作用机制释放并发挥作用。它进入其细胞内靶点核糖体并抑制蛋白质合成。对于杂合抗体无法结合的免疫球蛋白阴性细胞，毒性并未增强，游离的人免疫球蛋白G可竞争性阻断在携带免疫球蛋白的细胞系中观察到的增强效应。这些结果表明，杂合抗体可用于将活性剂携带至特定细胞类型的膜附近，从而选择性地增强其效应。
