Tohoku J. Exp. Med., 1999, 188 (4)

Review

Specific Targeting Immunotherapy of Cancer with Bispecific Antibodies

TOSHIO KUDO, MASANORI SUZUKI,1 YU KATAYOSE,1 MASAO SHINODA,1 NAOKI SAKURAI,1 HIDEAKI KODAMA,1 MASAHIKO ICHIYAMA, SHIN-ICHI TAKEMURA,1 HIROSHI YOSHIDA,1 HISAAKI SAEKI, SUSUMU SAIJYO,1 JITSUKO TAKAHASHI, TSUYOSHI TOMINAGA1 and SEIKI MATSUNO1

Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, and 1The First Department of Surgery, Tohoku University School of Medicine, Sendai 980-8574

  • In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor×anti-CD3 plus anti-tumor×anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor×anti-CD3, anti-tumor×anti-CD28, anti-tumor×anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.
    Key words--- bispecific antibody; specific targeting immunotherapy; MUC1; SEA
    © 1999 Tohoku University Medical Press

    Tohoku J. Exp. Med., 1999, 188, 275-288
    Address for reprints: Toshio Kudo, M.D., Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.
    e-mail: j23700@gen.cc.tohoku.ac.jp

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