Vitetta E S, Cushley W, Uhr J W
Proc Natl Acad Sci U S A. 1983 Oct;80(20):6332-5. doi: 10.1073/pnas.80.20.6332.
A strategy is described for improving the efficacy of ricin A chain-containing immunotoxins. Highly purified preparations of ricin A chain or ricin B chain were separately coupled to anti-human immunoglobulin antibodies and the conjugates (immunotoxins) were affinity purified to eliminate free chains. Mixtures of anti-Ig-A and anti-Ig-B immunotoxins markedly synergized in vitro in their ability to kill the Ig-bearing human lymphoma cell line Daudi. In contrast, A-chain- or B-chain-containing immunotoxins of irrelevant specificity did not synergize with anti-Ig-A or anti-Ig-B immunotoxins. This finding indicates that free A or B chains do not play a major role in the synergy and that the synergy is specific. Thus, synergy depends on the specificity of the two antibodies; the lectin binding ability of a B-chain-containing immunotoxin of irrelevant specificity does not suffice. This approach of delivering ricin A chain and B chain separately to a target cell may have significant advantages in killing cells that are not effectively killed by A-chain-containing immunotoxins alone.
本文描述了一种提高含蓖麻毒素A链免疫毒素疗效的策略。将高度纯化的蓖麻毒素A链或蓖麻毒素B链制剂分别与抗人免疫球蛋白抗体偶联，并对缀合物（免疫毒素）进行亲和纯化以去除游离链。抗Ig - A和抗Ig - B免疫毒素混合物在体外对携带Ig的人淋巴瘤细胞系Daudi的杀伤能力上具有显著协同作用。相比之下，具有无关特异性的含A链或B链免疫毒素与抗Ig - A或抗Ig - B免疫毒素没有协同作用。这一发现表明游离的A链或B链在协同作用中不起主要作用，且这种协同作用具有特异性。因此，协同作用取决于两种抗体的特异性；具有无关特异性的含B链免疫毒素的凝集素结合能力并不足够。这种将蓖麻毒素A链和B链分别递送至靶细胞的方法在杀伤单独使用含A链免疫毒素无法有效杀伤的细胞方面可能具有显著优势。
