IMPROVING TUMOR-TO-NORMAL-TISSUE RATIOS OF ANTIBODIES BY EXTRACORPOREAL IMMUNOADSORPTION BASED ON THE AVIDIN-BIOTIN CONCEPT - DEVELOPMENT OF A NEW TREATMENT STRATEGY APPLIED TO MONOCLONAL-ANTIBODIES MURINE L6 AND CHIMERIC BR96

BACKGROUND. Several strategies have been explored to accelerate monocl onal antibody (MAb) conjugate clearance without affecting intratumoral uptake. One of the most promising is extracorporeal immunoadsorption (ECIA), in which excess radiolabeled MAb circulating in blood is remov ed. METHODS. Extracorporeal immunoadsorption (ECIA) based on the avidi n-biotin concept enables direct adsorption of radiolabeled and biotiny lated MAb from plasma and consequently increases the tumor-to-normal-t issue uptake ratio by reducing background radioactivity in all radiose nsitive organs. Because the concept is based on an antibody's being bi otinylated prior to injection, the blood clearance efficiency is indep endent of the idiotype or isotype of the antibody employed. As a resul t, there is no need to develop new adsorption columns for each antibod y system used. We have technically simplified the method recently by r emoving biotinylated MAb directly from blood without separation from p lasma preceding the removal. The current study focused on both the dev elopment of ECIA and evaluating the effects of ECIA in terms of tumor targeting with two biotinylated radiolabeled MAbs that have different biokinetics, namely, murine MAb L6 and chimeric Mab BR96. RESULTS. The start time of ECIA should be determined for each MAb individually bef ore radioimmunotherapy and be based on previous tumor biokinetics. BR9 6 with rapid tumor targeting seems more suitable than L6 for the ECIA procedure; it allows the procedure to start earlier and thereby furthe r reduce whole body activity and exposure of critical organs to radiat ion. CONCLUSIONS. ECIA enables direct adsorption of radiolabeled and b iotinylated monoclonal antibody from blood and consequently increases the tumor-to-normal-tissue uptake ratio. The method is even applicable to both the internalizing and already highly tumor-selective BR96 in a syngeneic tumor model. (C) 1997 American Cancer Society.