Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using 125I-labeled anti-endoglin monoclonal antibodies

Endoglin (CD105), which is a component of the TGF-beta receptor complex, is highly expressed at the surface of proliferating human endothelial cells such as those of tumor vessels. In the present study, we tested the antitumor efficacy of I-125-labeled anti-endoglin monoclonal antibodies (MAbs), SN6f and SN6j, against s.c. tumors of MCF-7 human breast cancer cells in SCID mice by i.v. administration. SN6f and SN6j cross-react weakly with mouse endothelial cells, but show no significant reactivity with MCF-7 tumor cells. These MAbs are effectively internalized into the cells after binding to the cell surface antigen of endothelial cells. Four groups of SCID mice (n = 10 or 9 in each group) inoculated s.c. with 8 x 10(6) MCF-7 cells were treated with I-125-SN6f (10 mu Ci), (125I)-SN6j (10 mu Ci), a I-125-labeled isotype-matched control IgG (10 mu Ci) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both I-125-SN6f and I-125-SN6j showed significant growth suppression of the tumors, whereas the I-125-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either I-125-SN6f or I-125-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using I-125-labeled anti-endoglin MAbs. Int. J. Cancer 82:737-742, 1999. (C) 1999 Wiley-Liss, Inc.