McAb_3D_3与平阳霉素交联物的制备及其细胞杀伤实验

Preparation and the Cytotoxicity of Conjugate Composed of Pingyangmycin and Monoclonal Antibody against Human Lung Cancer

用ＤｅｘｔｒａｎＴ４０为中介体的方法交联抗人肺腺癌单抗３Ｄ３和平阳霉素（Ａ５），每克分子抗体可携带６８克分子的药物，交联物中抗体活性仍能达到１０－４水平，能较好地与靶细胞Ｌ－３４２结合。体外细胞毒实验，显示交联物和游离Ａ５对靶细胞５０％杀伤浓度分别为０．９μｍｏｌ／Ｌ和４．６μｍｏｌ／Ｌ，杀伤效果比游离Ａ５强５倍多。单抗对靶细胞几乎没有杀伤作用；无关抗体交联物的作用也很弱。交联物和游离Ａ５对非靶细胞ＭＧｃ－８０３的杀伤作用无明显差别。结果提示ＭＣＡｂ３Ｄ３具有良好的导向作用，能携带结合的Ａ５特异地杀伤肺腺癌Ｌ－３４２细胞，可作为临床抗肿瘤药物导向治疗的一种载体。

The conjugate of pingyangmycin (A5) and monclonal antibody3D3(MCAb3D3) against human lung cancer was prepared with dextran T40 as the mediator.The molar ratio of A5 McAb3D3 in the conjugate was 68:1 the titer of the conjugate was remained at 10-4.In vitro,the cytotoxicity of the conjugate and free A5 yieded IC50 of 0.9μmol/L and 4.6μmol/L,respectivel.The conjugate was fivetimes stronger than free A5 The cytotoxicity of the conjugate on non-target cells MGc-803 was much weaker and similar to that of. free A5.There is no doubt that MCAb3D3 had targeting activity and could kill or damage tumor cells specifically and could be taken as a kind of vector in studies of clinical targeting therapy.