单克隆抗体B159－表阿霉素结合物的研制及活性鉴定

Preparation and Biological Activity of Monoclonal Antibody B159-Epirubicin Conjugate

本文报道蒽环类抗癌新药表阿霉素通过支联剂葡聚糖Ｔ１０与Ｂ淋巴细胞白血病单克隆抗体Ｂ１５９交联组成的Ｂ１５９－Ｄｅｘ－ＥＰＩ结合物，每克分子抗体可携带１４克分子的药物。在制备过程中结合物中抗体活性无损失。结合物对靶细胞具有较强的选择性细胞毒作用（ＩＣ５０为０．８８μｇ／ｍｌ），明显优于游离表阿霉素（ＩＣ５０为２．７μｇ／ｍｌ）及无关抗体结合物（ＩＣ５０＞３０μｇ／ｍｌ），对非靶细胞毒性较弱（ＩＣ５０＞３０μｇ／ｍｌ）。

Epirubicin(EPI),a new anthracycline anticancer drug, was linked covalently to monoclonal antibody B159 which was against human B lymphocytic leukemia with use of dextran(Dex) as a small molecular linker.The molar ratio of B159: EPI was 1:14 in the conjugate cellular ELISA(CELISA) and living cell immunofluorescence test revealed that B159-Dex-EPI conjugate retained substantially the origional immunological activity of the B159.In virto,the cytotoxicity of the conjugate (IC50 0.88 μg/ml) against Raji cell line was stronger than either EPI(IC50 2.7 μg/ml) or NIgGDex-EPI(IC50>30 μp/ml).The toxicity of B159-Dex-EPI to nontarget cell lines, K562 and Sp2/0,was low,with IC50 values of over 30 μg/ml.