Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-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 (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 x 10(6) MCF-7 cells were treated with (125)I-SN6f (10 microCi), (125)I-SN6j (10 microCi), a (125)I-labeled isotype-matched control IgG (10 microCi) 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 anti-endoglin MAbs.
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
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Tabata
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Kondo
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Haruta
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Seon
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology; D002478:Cells, Cultured; D000071063:Endoglin; D004727:Endothelium / Q000276:immunology / Q000528:radiation effects; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; C064206:ENG protein, human; D000071063:Endoglin; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1