Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using125I-labeled anti-endoglin monoclonal antibodies

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Abstract
Endoglin (CD105), which is a component of the TGF-β 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 125I-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 × 106 MCF-7 cells were treated with 125I-SN6f (10 μCi), 125I-SN6j (10 μCi), a 125I-labeled isotype-matched control IgG (10 μCi) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both 125I-SN6f and 125I-SN6j showed significant growth suppression of the tumors, whereas the 125I-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either 125I-SN6f or 125I-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using 125I-labeled anti-endoglin MAbs. Int. J. Cancer 82:737–742, 1999.