MAB-CYTOKINE R-ALPHA FUSIONS TO DELIVER ARMED LIGAND

描述(改编自申请人的摘要)：传统方法 给与药物和其他治疗药物来治疗 疾病通常使用全身途径。这暴露了病理性细胞 人群和正常组织对这些病原体的非特异性。如果处于活动状态 治疗某种疾病的药物只有一个低的治疗指数，治疗可以 要么无效，要么伴随着严重的副作用。这 各种恶性肿瘤(如肺癌)的发病情况 肺、乳腺、前列腺和结肠)，以及各种 免疫调节和炎症状态。在这些后一种情况中 疾病状态，如自身免疫性糖尿病状态，器官 移植，骨髓移植，炎症性肠病， 以及其他自身免疫性疾病(例如系统性红斑狼疮、 类风湿性关节炎)。 在此应用程序中，通过一种创新的方法解决了该问题 药物或其他药物的细胞内递送最终可能是 适用于上述疾病的诊断和治疗。这 该方法涉及到利用由单个 链式单抗与部分细胞因子的配体结合区 感受器。这种融合蛋白将被用来靶向致病细胞 人口。与同源物相关联的治疗或诊断药物 然后将给予细胞因子。这充分利用了 配体/受体的相互作用；这些作用的快速、有效的内化 受体，并允许高水平的细胞表面抗原成为靶点 大幅增加细胞因子受体的数量超过其最低水平 背景级别。具体地说，该应用程序旨在将 研究人员通过构建和表达所做的初步努力 抗体-受体融合蛋白及其同源物的臂形式 配基。在构建和表达后，将对其功能进行测试 在体外进行临床前和临床评估的最终途径 各种疾病模式和病情。

DESCRIPTION (Adapted from the applicant's abstract): Traditional approaches to administration of drugs and other therapeutic agents for the treatment of disease often use a systemic route. This exposes pathologic cell populations and normal tissues nonspecifically to these agents. If active agents for a given disease have only a low therapeutic index, treatment may either be ineffective or be associated with serious side effects. This situation obtains for a wide range of malignancies (such as cancers of the lung, breast, prostate and colon), as well as for a variety of immune-mediated and inflammatory conditions. Among these latter conditions are disease states such as autoimmune diabetic states, organ transplantation, bone marrow transplantation, inflammatory bowel disease, and other autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis). The problem is addressed in this application with an innovative approach to intracellular delivery of drugs or other agents that could ultimately be applied to the diagnosis and therapy of the diseases listed above. This approach involves the utilization of fusion molecule consisting of a single chain monoclonal antibody and the ligand-binding domain of selected cytokine receptors. This fusion protein will be used to target pathogenic cell populations. Therapeutic or diagnostic agents linked to the cognate cytokine will then be given. This capitalizes on the specificity of the ligand/receptor interactions; the rapid, efficient internalization of these receptors, and allows for a high-level cell surface antigen to be targeted to substantially increase the number of cytokine receptors over their low background level. This application, specifically, seeks to advance the initial efforts made by researchers by constructing and expressing antibody-receptor fusion proteins as well as armed forms of the cognate ligands. After construction and expression, their function will be tested in vitro on an ultimate path towards pre-clinical and clinical evaluation in a variety of disease models and conditions.