三种柔红霉素-白血病单抗免疫偶合物特性比较

用 3种方法将纯化的 Mc Ab1A1 与柔红霉素 (DNR)偶联 ,直接交联法制备的 Mc Ab1A1 - DNR偶合物克分子比为 1∶ 5 2 ,抗体活性有所下降 ,药物活性保留 84.6 % ;顺乌头酸酐法制备的 Mc Ab1A1 - CADNR偶合物克分子比为 1∶ 2 7,保持了较好的抗体活性 ,药物活性保留 5 0 % ;间接法制备的 Mc Ab1A1 - PAD- DNR偶合物克分子比为 1∶ 437,保持了较好的抗体活性 ,药物活性保留 91.6 %。 Mc Ab1A1 - PAD- DNR偶合物对 U937靶细胞的杀伤作用最强 ,Mc Ab1A1 - DNR次之。实验中观察到 ,L owry法不能用于含 DNR偶合物中抗体蛋白含量的测定 ,活细胞 EL ISA法不能用于含 DNR偶合物中抗体活性测定。

Comparison of Characteristics of 3 Kinds of DNR-Anti-Leukemia McAb Immunoconjugates

The purity of McAb1A 1 to acute nonlymphocytic M 5 leukemia reached 99.9% after being purified by ion exchange and gel filtration chromatographys. Three kinds of immunoconjugates, McAb1A 1 DNR, McAb1A 1 CADNR and McAb1A 1 PAD DNR, were prepared by direct coupling, cis aconity/linkage and indirect coupling respectively. The molar ratios of the 3 immunoconjugates were 1∶52, 1∶27 and 1∶437 respectively, and 84.6%,50% and 91.6% of drug activities of them were retained respectively. Though the antibody activitiy of McAb1A 1 PAD DNR was significantly decreased, no significant decrease was observed in those of McAb1A 1 CADNR and McAb1A 1 PAD DNR. McAb1A 1 PAD DNR was the most effective in killing U 937 target cells. The authors found that Lowry method could not be used for determining the antibody protein contents in the conjugates containing DNR, and live cell ELISA could not be used for determining the antibody acitivities in them.