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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。
MAb-737 that binds specifically to the B cell class Ia antigen and ricin is disulfide bonded to the immunotoxin ricin-737. In vitro, the immunotoxin showed selective killing of Raji cells in the Burkitt’s lymphoma cell line with B cell antigen in the presence of 0.1 M lactose in vitro. The median lethal concentration (IC 50) was 5 × 10 ~ (-11) M. Under the same conditions, K_ (562) of control cells without target antigen showed no significant killing, and the IC 50 was 10 -3 M, which was 500 times lower than the control. The free toxin IC 50 (IC 50) is 5 × 10 -3 M, which is 1000 times less toxic than immunotoxin. Kinetic studies have shown that immunotoxins can inhibit the proliferation of target cells for 1 hour and kill more significantly as the treatment time prolongs. The results suggest that the immunotoxin ricin-737 has a strong selective ability to kill target cells and can be used as a candidate drug for tumor therapy.