ENGINEERING CELL TYPE SPECIFIC TOXINS

单克隆抗体选择性结合肿瘤细胞分化 抗原在体外和体内。 由于自然效应机制通常 不介导单克隆抗体结合细胞的杀伤， 设计出将剧毒蛋白质与抗体连接的方法 选择性地杀死肿瘤细胞。 我们成功地开发了 免疫毒素在体内应用的几种新方法。 (1)克隆 毒素，然后在基因水平上改变它们的结构， 靶细胞毒性;（2）制备基因工程 用于人类脑肿瘤患者临床试验的免疫毒素;（3） 用抗CD 4抗体预防针对免疫毒素的免疫应答 （4）使用人细胞毒性蛋白质，如RNA酶连接的 选择性靶向细胞的抗体;（5）了解 人类核糖核酸酶神经毒素的机制;和（6）发现核糖核酸酶， 在体内阻断HIV感染。

Monoclonal antibodies selectively bind tumor cell differentiation antigens in vitro and in vivo. Since natural effector mechanisms often do not mediate killing of monoclonal antibody bound cells we have devised methods of linking extremely toxic proteins to the antibodies to selectively kill tumor cells. We have succeeded in developing several new approaches to apply immunotoxins in vivo. (1) Cloning toxins, then altering their structure at the gene level to decrease non target cell toxicity; (2) preparation of genetically engineered immunotoxins for clinical trials of human brain tumor patients; (3) prevention of an immune response against immunotoxins with anti-CD4 antibodies; (4) use of human cytotoxic proteins such as RNase linked to antibodies to selectively target cells; (5) understanding the mechanism of human RNase neurotoxins; and (6) discovering that RNases block HIV infection in vivo.