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Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using 125 I‐labeled anti‐endoglin monoclonal antibodies
Author(s) -
Tabata Masahiro,
Kondo Masao,
Haruta Yuro,
Seon Ben K.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990827)82:5<737::aid-ijc18>3.0.co;2-8
Subject(s) - radioimmunotherapy , endoglin , monoclonal antibody , antibody , cancer research , antigen , monoclonal , biology , pathology , microbiology and biotechnology , medicine , immunology , stem cell , genetics , cd34
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 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 μCi), 125 I‐SN6j (10 μCi), a 125 I‐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 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. Int. J. Cancer 82:737–742, 1999. © 1999 Wiley‐Liss, Inc.