title: Specific targeting immunotherapy of cancer with bispecific antibodies.
abstract: 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 x anti-CD3 plus anti-tumor x 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 x anti-CD3, anti-tumor x anti-CD28, anti-tumor x 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.
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. j23700@gen.cc.tohoku.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Katayose
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.forename: N
authors.initials: N
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Ichiyama
authors.forename: S
authors.initials: S
authors.lastname: Takemura
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Saeki
authors.forename: S
authors.initials: S
authors.lastname: Saijyo
authors.forename: J
authors.initials: J
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Tominaga
authors.forename: S
authors.initials: S
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000628:therapy
chemical_list: D018033:Antibodies, Bispecific