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Identification of tumor vascular antigens by monoclonal antibodies prepared from rat‐tumor‐derived endothelial cells
Author(s) -
Ohizumi Iwao,
Tsunoda Shinichi,
Taniguchi Kenji,
Saito Hiroyuki,
Esaki Keiko,
Koizumi Keiichi,
Makimoto Hiroo,
Wakai Yukiko,
Matsui Junji,
Tsutsumi Yasuo,
Nakagawa Shinsaku,
Utoguchi Naoki,
Ohsugi Yoshiyuki,
Mayumi Tadanori
Publication year - 1998
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(19980812)77:4<561::aid-ijc15>3.0.co;2-9
Subject(s) - monoclonal antibody , antigen , immunohistochemistry , antibody , biology , fibrosarcoma , microbiology and biotechnology , endothelial stem cell , pathology , cancer research , in vitro , immunology , medicine , biochemistry
We have reported the isolation and specific in vitro properties of tumor‐derived endothelial cells (TEC) from rat KMT‐17 fibrosarcomas transplanted into rats. To develop antibody‐based tumor vascular targeting therapy for solid tumors, we have generated monoclonal antibodies (MAbs) using passive immunization of outside‐out membrane vesicles of rat epididymal‐fat‐pad‐derived capillary endothelial cells (FCEC) followed by active immunization of those of rat TEC. The MAbs produced were screened against TEC and FCEC. Of all cultured hybridomas, 75 (3.3%) of the secreted MAbs preferentially recognized TEC. We selected a total of 7 MAbs which detected antigens highly abundant in TEC, although 5 of the 7 MAbs were weakly positive for FCEC in cell‐ELISA and FACS analyses. The antigens recognized by these MAbs, with the exception of MAb TES‐7, were present on endothelial cells of tumor blood vessels in KMT‐17 fibrosarcoma tissues, as shown by immunohistochemical analysis. Antigens of 40‐ and 80‐kDa were recognized by MAbs TES‐1, 7, 17, 21 and 26 and by MAbs TES‐23 and 27 respectively. Although the function of these antigens, which are preferentially expressed on rat tumor‐derived endothelial cells, is still unknown, we believe that future studies of such antigens will help elucidate the role of endothelial cells in tumor vasculature. Our results indicate that MAbs may provide a novel tool for the development of antibody‐based therapy targeting tumor vasculature. Int. J. Cancer 77:561–566, 1998. © 1998 Wiley‐Liss, Inc.