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.
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| Rehlaender, B N; Cho, M J (1998) Antibodies as carrier proteins. Pharm Res 15:1652-6 |
