抗人B细胞MAb-737与蓖麻毒蛋白偶联物对肿瘤细胞选择性杀伤

具有针对B细胞类Ia抗原特异反应性MAb-737与蓖麻毒蛋白通过二硫键连接成免疫毒素ricin-737。体外0.1M乳糖存在时,此免疫毒素对含B细胞抗原的Burkitt氏淋巴瘤细胞系Raji细胞表现出选择性地强力杀伤,半数杀伤浓度(IC_(50))为5×10~(-11)M。同样条件,对不含靶抗原的对照细胞K_(562)没有显著杀伤,IC_(50)为10~(-3)M,毒性比前者低500倍。游离毒蛋白IC_(50)为5×10~(-3)M,比免疫毒素毒性低1000倍。动力学研究表明,免疫毒素作用1小时就可抑制靶细胞的增殖,并随处理时间延长,杀伤更趋显著。结果提示,免疫毒素ricin-737具有强烈地选择性杀伤靶细胞能力,可成为肿瘤治疗的候选药物。

SELECTIVE CYTOTOXICITY OF RICIN-737 (A MAB-737 AND RICIN CONJUGATE WITH ANTI-HUMAN B CELL SPECIFITY) TO TUMOR CELLS

A monoclonal antibody 737, directed to la-like antigens of human B lymphocytes, was covalently conjugated with ricin (a potent plant toxin) by a disulfide bond to forman immunotoxin (ricin-737). The MAb-737 is highly specific to Raji cells, a member ofBurkitt's lymphoma cell line. Immunoflourescence positive rate of Raji cells with MAb-737 is over 90% at the concentration of 10-5M/L. After conjugation, the MAb-737 component of the immunotoxin still retains its specificity to Raji cells. The cytotoxicity of ricin-737 to Raji cells is 108 times that of native ricin in vitro in the presence of 0.1M lactose. Under the same experimental condition, the cytotoxicity to K562 cells is relatively insignificent, being only 1/500 of that to Raji cells. The results suggest that ricin-737 could selectively kill human B lymphocytes and might be a potential therapeutic agent for human B lymphoma and leukemia.