制备抗表皮生长因子受体单克隆抗体(EQ75)与化疗药物阿霉素(ADR)、免疫偶联物(EQ75-ADR)，研究该偶联物对人表皮癌A431的抑瘤作用和小鼠的副作用,为最终应用于临床打下基础。方法：用改进的戊二醛方法制备EQ75-ADR，MTT法检测EQ75-ADR对人表皮癌细胞A431和对照细胞人羊膜细胞Wish的48h和2h细胞毒作用，建立荷人表皮癌裸鼠模型和C57BL/6J小鼠模型，观察EQ75-ADR的抑瘤作用，比较EQ75-ADR和ADR对C57BL/6J的副作用。结果： EQ75-ADR对 A431细胞有明显的细胞毒作用，体外作用48h，EQ75-ADR对A431细胞的杀伤分别是EQ75，ADR和EQ75与ADR混合物(EQ75+ADR)的50倍，14倍和10倍，而EQ75-ADR对Wish细胞的杀伤只有ADR和EQ75+ADR的1/10，对Wish细胞的杀伤只有对A431细胞的1/300，2 h作用得到类似结果。EQ75-ADR显著抑制裸鼠体内肿瘤的生长，抑制率高达92.2% ( P <0.01)，对C57BL/6J小鼠的副作用明显低ADR。结论： EQ75-ADR具有选择性杀伤作用，在体外和体内对表皮癌均有显著抑制作用，副作用小，在肿瘤生物治疗中具有潜在的应用价值。

To prepare an immunoconjugate of anti-EGFR monoclonal antibody (EQ75) and adriamycin (ADR) and to investigute it's inhibitory effect on human epidermoid carcinoma (A431) in vitro and in vivo and it's side effect on C57BL/6J mice. Methods: The immunoconjugate (EQ75-ADR) was prepared with animproved glutaraldehyde conjugate method and the cytotoxicity effects of EQ75-ADR on A431 cells and Wish cells were measured by MTT assay. A431 tumor-bearing nude mice and C57BL/6J experimental model were established and were used for testing the inhibitory effects of EQ75-ADR. The side effect of EQ75-ADR was compared with ADR. Results: The EQ75-ADR showed specific cytotoxicity on A431cells, the cytotoxicity of EQ75-ADR was 50-fold, 14-fold and 10-fold more efficient than that of EQ75, ADR and mixture of EQ75 and ADR (EQ75+ADR) respectively. The effect of EQ75-ADR on with cells was 10-fold less efficient than that of ADR and EQ75+ADR. As compared with the cytoxicity effect of EQ75-ADR on Wish cells with A431 cells, it showed 300-fold less efficient. Similar cytotoxicity results were shown in 2 h treatment experimental group. The EQ75-ADR exhibited significant anti-tumor activity on tumor-bearing nude mice, and the inhibition rate is 92.2% (P<0.01). As compared with ADR, it's side effect was much lower. Conclusion: The EQ75-ADR exhibited targeted delivery and striking anti-tumor activity in vitro and in vivo and this approach appears a promising future for clinic purpose.

* 本课题受上海市科委科技发展基金(954119028)资助