Monoclonal antibody (MAb)
B72.3 has been linked successfully to several
radionuclides forming stable complexes and analyzed in vitro and in vivo without significant loss of its immunoreactivity. Previous studies have demonstrated that radioiodinated
B72.3 can selectively bind to human
colorectal carcinomas grown in athymic mice. The same successful localization has been obtained more recently in clinical trials in patients with metastatic
colorectal carcinomas. The high degree of selective binding of this MAb has led us to investigate its potential as a radioimmunotherapeutic agent. Athymic mice bearing human colon
carcinoma xenografts were injected with either 300 or 500 microCi of 131I-B72.3
IgG to assess the effect o the radiolabeled MAb on the
tumor growth as well as potential toxic side effects in vital organs. In mice treated with the 131I-B72.3
IgG, a marked inhibition of the growth of the human colon
carcinoma xenografts was noticed in comparison with control mice injected with PBS or control mice that received unlabeled
B72.3 IgG. The
tumors from these control mice weighed 2.7 to 3.7 times more than the
tumors from the treated mice
at 17 days post-inoculation of the radiolabeled MAb. Autoradiographic studies demonstrated a heterogeneous distribution of radioactivity throughout the
tumor mass at 11 days post-administration of MAb. With time, the periphery of the
tumor contained significantly less radioactivity than the medial areas composed of predominantly nonviable tissue; these findings suggest that the more biologically active peripheral
tumor zones, with higher mitotic rates, could have partially escaped the radiation effect of the single dose administered. The
tumor cells could have continued dividing when the levels of circulating radiolabeled
monoclonal antibody had decreased. Toxicity was readily evident in the mice injected with the high-dose regimen (500 microCi), with confirmed bone marrow aplasia that proved lethal for 2 of 10 animals. The lower dose (300 microCi) resulted in a bone marrow suppression of approx. 50% of the cells, which proved to be non-lethal. The
tumors in the treated mice showed extensive
necrosis caused by the lethal dose of 131I-B72.3 that irreversibly damaged the cells. Radiation-induced terminal differentiation of cells was also found as manifested by the drastically decreased mitotic count (0-2 vs. 12-14 per 10 high power fields seen in control
tumors) in treated animals.