BISPECIFIC ANTIBODY FOR DIRECTED DELIVERY OF PALYTOXIN

描述：(改编自申请者的摘要)相当感兴趣 一直专注于治疗性药物的生产和表征 免疫结合物。这种杂化分子通常由一种单克隆性 带有共价结合的毒素、药物或放射性同位素的抗体。其中一些 这些药物已被证明在临床上对免疫抑制有用。 或者癌症治疗。然而。这些共价连接的免疫结合物 也存在缺陷。毒素与药物的共价修饰 通常会降低它们的效力。此外，使用的许多蛋白质毒素 为此目的是免疫原性。精选的另一种方法 细胞毒剂的传递是使用双特异性抗体。最近 报道的方法允许抗体片段的选择性连接，从而 高产率地生产了具有双重抗原特异性的F(ab‘Gamma)2。 孢子毒素是所描述的最有效的非蛋白质类毒素，是 相对分子质量较低(2678.5克/摩尔)。这些属性使 芽孢杆菌毒素是一种有吸引力的定点细胞消融候选物质 治疗。这个组织已经准备好了针对 孢子虫毒素。申请人提议构建双特异性F(ab‘Gamma)2 来源于这些单抗和单抗 与CD4人类T细胞抗原发生反应。这些双特异性抗体将 在体外测试对表达CD4的细胞的定向选择性杀伤 抗原。

DESCRIPTION: (Adapted from the Applicant's Abstract) Considerable interest has been focussed on the production and characterization of therapeutic immunoconjugates. Such hybrid molecules usually consist of a monoclonal antibody with covalently attached toxin, drug, or radioisotope. Some of these agents have been shown to be clinically useful for immunosuppression or cancer treatment. However. these covalently linked immunoconjugates also suffer from drawbacks. Covalent modification of toxins and drugs often reduces their potency. In addition, many of the protein toxins used for this purpose are immunogenic. Another approach for the selective delivery of cytotoxic agents is to use bispecific antibodies. Recently reported methods allow selective linkage of antibody fragments, such that F(ab' gamma)2 with dual antigen specificity are produced in high yield. Palytoxin is the most potent non-proteinaceous toxin described and is of comparatively low molecular weight (2678.5g/mol). These attributes make palytoxin an attractive candidate for site-directed cell ablative therapies. This organization has prepared monoclonal antibodies to palytoxin. The applicant proposes to construct bispecific F(ab' gamma)2 derived from these monclonal antibodies and from monoclonal antibodies reactive with CD4 human T-cell antigen. These bispecific antibodies will be tested in vitro for directed selective killing of cells expressing CD4 antigen.