Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using 125I-labeled anti-endoglin monoclonal antibodies
✍ Scribed by Masahiro Tabata; Masao Kondo; Yuro Haruta; Ben K. Seon
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 162 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Endoglin (CD105), which is a component of the TGF- 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 125 I-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 ؋ 10 6 MCF-7 cells were treated with 125 I-SN6f (10 Ci), 125 I-SN6j (10 Ci), a 125 I-labeled isotype-matched control IgG (10 Ci) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both 125 I-SN6f and 125 I-SN6j showed significant growth suppression of the tumors, whereas the 125 I-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either 125 I-SN6f or 125 I-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using 125 I-labeled antiendoglin MAbs.