title: Development of humanized monoclonal antibody TMA-15 which neutralizes Shiga toxin 2.
abstract: A murine monoclonal antibody (MAb), VTm1.1, specifically recognizing and neutralizing Shiga toxin 2 (Stx2), was obtained. To prevent a humoral response against murine antibody when used clinically, a humanized antibody was constructed by combining the complementarity-determining regions of VTm1.1 with human framework and constant regions. In addition, several amino acids in the framework were changed to improve the binding affinity of the antibody and further reduce its potential immunogenicity. The humanized antibody, TMA-15, recognized the B-subunit of Stx2 and had affinity for Stx2 of 3.3 x 10(-9) M, within two-fold of that of the original murine antibody. TMA-15 neutralized the cytotoxicity of Stx2 and several different Stx2 variants in vitro, and it completely protected mice from death in a Stx2-challenged mice model. These results suggest that TMA-15 will have clinical potency in Stx-producing Escherichia coli infections, including E. coli O157 infections.
authors.affiliation: Teijin Institute for Biomedical Research, Teijin Limited, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan. t.kimura@teijin.co.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Man Sung
authors.initials: MS
authors.lastname: Co
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Vasquez
authors.forename: Sharon
authors.initials: S
authors.lastname: Wei
authors.forename: Hattie
authors.initials: H
authors.lastname: Xu
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tani
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Yoh-Ichi
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakao
authors.forename: Tae
authors.initials: T
authors.lastname: Takeda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009101:Multiple Myeloma; D016415:Sequence Alignment; D022641:Shiga Toxin 2 / Q000276:immunology*; D013154:Spleen
chemical_list: D000911:Antibodies, Monoclonal; D022641:Shiga Toxin 2