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目的 研制一种以单抗Fab′片段为基础的抗肿瘤导向药物。方法 制备单抗 3A5Fab′片段及其与平阳霉素 (PYM )偶联物Fab′ PYM后 ,测定Fab′ PYM与肿瘤细胞的免疫反应性、偶联物中PYM的抑菌活性、对肿瘤细胞的杀伤作用和体内抑瘤作用。结果 Fab′及Fab′ PYM保持了与靶细胞C2 6的免疫反应性 ;偶联物中PYM的抑菌活性为游离PYM的 15 % ;Fab′ PYM对C2 6细胞的杀伤作用强于PYM ;对非靶细胞KB的杀伤作用与PYM相似 ;ip和iv给药 ,Fab′ PYM对小鼠皮下接种的肠癌 2 6生长抑制作用均强于 3A5 PYM和PYM。结论 Fab′ PYM具有比PYM及 3A5 PYM更强的体内外抗肿瘤作用
Objective To develop an anti-tumor drug based on Fab′ fragment of monoclonal antibody. Methods After preparing monoclonal antibody 3A5Fab’ fragment and its conjugate with Pingyangmycin (PYM) Fab’ PYM, the immunoreactivity of Fab’ PYM and tumor cells, the antibacterial activity of PYM in conjugates, and the tumor cells were determined. Killing effect and anti-tumor effect in vivo. Results The Fab′ and Fab′ PYM maintained the immunoreactivity with target cell C26; the antibacterial activity of PYM in the conjugate was 15% of that of free PYM; the Fab′ PYM had stronger killing effect on C2 6 cells than PYM; The killing effect of KB in non-target cells was similar to that of PYM. In ip and iv administration, Fab′ PYM inhibited the growth of subcutaneously inoculated intestinal cancer 26 was stronger than 3A5 PYM and PYM. Conclusion Fab′ PYM has stronger anti-tumor effect in vitro and in vivo than PYM and 3A5 PYM