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

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.