TARGETED CELLULAR CYTOTOXICITY

1.建立了小鼠乳腺癌模型，验证了该方法的可行性。 靶向同基因T细胞根除移植实体瘤 肺转移。当给荷瘤小鼠服用时，基因上的 基因工程双特异性抗体可以延缓肿瘤的生长和 延长小鼠的存活时间。 2.构建了一种基因工程单链双特异性分子 在哺乳动物细胞和细菌中产生，这些细菌 在体外将小鼠T细胞重定向至溶解靶细胞，为ng/ml 级别。 3.CD44成为人NK细胞的细胞毒触发分子 用IL-2或IL-12刺激24小时后。CD44依赖的裂解 涉及丝氨酸-苏氨酸和酪氨酸激酶，并激活 CD44伴随着它与其他蛋白质的结合，包括一种 这是酪氨酸磷酸化。类似的研究表明，CD69 4天后成为PBL亚群上的细胞毒触发分子 激活。

1. A murine mammary carcinoma model has been used to test the ability of targeted syngeneic T cells to eradicate transplanted solid tumor lung metastases. When given to tumor bearing mice, a genetically engineered bispecific antibody retards the growth of tumors and prolongs survival of mice. 2. A genetically engineered single chain bispecific molecule has been produced in mammalian cells and in bacteria which specifically redirects mouse T cells to lyse target cells in vitro, at ng/ml levels. 3. CD44 becomes a cytotoxic triggering molecule on human NK cells after 24 hr stimulation with IL-2 or IL-12. CD44-dependent lysis involves both serine-threonine and tyrosine kinases, and activation of CD44 is accompanied by its binding to other proteins, including one that is tyrosine phosphorylated. Similar studies have shown that CD69 becomes a cytotoxic triggering molecule on subsets of PBL after 4 days activation.