[RE-186]-LABELED MOUSE AND CHIMERIC MONOCLONAL-ANTIBODY 323 A3 - A COMPARISON OF THE EFFICACY IN EXPERIMENTAL HUMAN OVARIAN-CANCER/

We have investigated whether [Re-186]-labeled chimeric monoclonal anti body 323/A3 (MAb c-323/A3) is as effective as [Re-186]-labeled mouse 3 23/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xeno grafts OVCAR-3 and FMa. [Re-186] was conjugated to MAbs with the use o f the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MA b molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With t hese molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A 3 and its blood clearance. Both [Re-186]-c-323/A3 and [Re-186]-m-323/A 3 were comparable in the inhibition of the tumor growth when higher pr otein doses were used. Together with the expected lower immunogenicity , our results imply that c-323/A3 is preferable for use in [Re-186]-ra dioimmunotherapy in ovarian cancer patients. (C) 1998 Elsevier Science Inc.