Biodistribution of antibodies after intraperitoneal or intravenous injection and effect of carbohydrate modifications

ABSTRACT-These studies were designed to improve the strategy for intraperitoneal immunotherapy of human ovarian carcinoma with monoclonal antibodies (MAbs). Since ovarian tumor cells generally appear to be confined to the peritoneal cavity, regional therapy is appropriate and can reduce the need for strictly tumor-specific MAbs. In normal mice, with the use of radioiodine-labeled MAbs, transfer from peritoneal cavity to blood was found to be very rapid, within hours, and this transfer was delayed slightly by increasing the volume injected. The presence of ascitic fluid in mice greatly delayed the rate of transfer. For reduction of possible toxicity for normal cells outside the peritoneal cavity, the hepatic receptor for desialylated serum glycoproteins was used. Neura-minidase treatment of all major mouse immunoglobulin classes and subclasses, including IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA, did not cause their rapid blood clearance, although similar treat