BISPECIFIC ANTIBODY FOR DIRECTED DELIVERY OF PALYTOXIN

描述：（改编自申请人的摘要）相当大的兴趣 一直专注于治疗药物的生产和表征 免疫缀合物。 这种杂合分子通常由单克隆抗体组成。 与毒素、药物或放射性同位素共价连接的抗体。 一些 这些药物已显示出在临床上可用于免疫抑制 或癌症治疗。 然而. 这些共价连接的免疫缀合物 也有缺点。 毒素和药物的共价修饰 往往会降低其效力。 此外，许多使用的蛋白质毒素 是免疫原性的。 另一种选择性的方法 细胞毒性剂的递送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， 以高产率生产具有双重抗原特异性的F（ab'γ）2。 海葵毒素是所描述的最有效的非蛋白质毒素， 相对较低的分子量（2678.5g/mol）。 这些属性使 一种有吸引力的定点细胞消融候选物 治疗 该组织已经制备了单克隆抗体， 海葵毒素 申请人提出构建双特异性F（ab'γ）2 衍生自这些单克隆抗体和衍生自单克隆抗体 与CD 4人T细胞抗原反应。 这些双特异性抗体将 在体外测试对表达CD 4的细胞的定向选择性杀伤 抗原的

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.