Radioimmunotherapy of solid
malignancies using directly labelled 90Y-monoclonal
antibodies has been associated in clinical trials with dose-limiting bone marrow toxicity. Our objective in this study was to evaluate the efficacy and toxicity of an alternative two-step pre-targeted
radioimmunotherapy protocol for the treatment of human
colon cancer. The two-step protocol consisted of administration of the tumour-associated
glycoprotein (TAG-72)
monoclonal antibody CC49 conjugated to
streptavidin, followed by administration of
90Y-DOTA-biotin. Swiss nu/nu athymic mice bearing subcutaneous LS174T human
colon cancer xenografts were injected intraperitoneally with streptavidin-CC49 (250 micrograms), followed 40 h later by an
intravenous injection of
90Y-DOTA-biotin (900 microCi, 40 micrograms). Tumour growth was measured over 25 days and compared with that in control mice receiving no treatment. Bone marrow and normal tissue toxicity was determined by peripheral blood leucocyte counts and by monitoring the
body weight of the animals. Pre-targeted
radioimmunotherapy resulted in a modest (30-40%) decrease in the mean tumour growth rate in treated mice compared to control animals. There was no change in
body weight following treatment and peripheral blood leucocyte counts remained within the normal range. Pre-targeted
radioimmunotherapy was safe at administered amounts of 90Y radioactivity, which were at least nine-fold higher than those previously determined to be lethal using directly labelled 90Y-monoclonal
antibodies. The results of this study are promising for the application of pre-targeted
radioimmunotherapy using streptavidin-CC49 and
90Y-DOTA-biotin for the treatment of advanced
colorectal cancer in humans.