CANCER THERAPY THROUGH REDIRECTING NATURAL ANTIBODIES

描述：人类和旧世界灵长类动物自然产生一个大的 识别表位Gal α 1->3Gal的抗体的量。 的 目前的建议是测试抗体是否可以针对叶酸 通过小分子量靶向表达受体的癌细胞 由二糖和叶酸组成的配体，称为 FGG缀合物。 当被递送到靶细胞时，抗体被 预期通过补体介导的裂解或 抗体依赖性细胞介导的细胞毒性。 概念的可行性将专门用于治疗卵巢癌 癌症是最终目标。 众所周知，卵巢上皮细胞 癌细胞过度表达叶酸受体。 在FGG受体 结合物的合成，本研究将首先建立 FGG缀合物与细胞表面受体结合的特异性 以及抗Gal抗体，然后阐明细胞毒性 机制 对于这一系列的实验，叶酸，受体表达 将使用来源于人卵巢癌的IGROV 1细胞。 以来 FGG缀合物将最终腹膜内施用，其是 必须绘制腹膜液的免疫学特征， 癌症患者。最后，该研究将证明IGROV 1 在FGG存在下，腹膜液中的细胞被杀死 共轭 拟定商业应用： 未提供拟议的商业应用。

DESCRIPTION: Human and Old World primates naturally produce a large amount of antibodies which recognize an epitope Gal alpha 1-->3Gal. The present proposal is to test if the antibodies can be directed to folate receptor-expressing cancerous cells by means of a small MW targeting ligand that consists of the disaccharide and folic acid, referred to as FGG conjugate. When delivered to the target cell, the antibodies are expected to cause cell death by either complement-mediated lysis or antibody-dependent cell-mediated cytotoxicity. The concept feasibility will be tested specifically for treating ovarian cancer as the ultimate goal. It is known that the ovarian epithelial carcinoma cells overexpress the folate receptor. After the FGG receptor conjugate is synthesized, this study will first establish the specificity of binding of the FGG conjugate to the cell surface receptor as well as the antiGal antibodies, followed by elucidation of cytotoxic mechanism. For this series of experiments, folate, receptor-expressing IGROV1 cells derived from human ovarian cancer will be used. Since the FGG conjugate will be eventually administered intraperitoneally, it is imperative to map the immunological profile of the peritoneal fluid from the cancer patients. Finally the study will demonstrate that IGROV1 cells are killed in the peritoneal fluid in the presence of the FGG conjugate. PROPOSED COMMERCIAL APPLICATION: Proposed commercial application not available.