2002
DOI: 10.1089/153685902760173872
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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 … Show more

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Cited by 29 publications
(27 citation statements)
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“…With this in mind, we developed HuMAbs to neutralize Stx (17)(18)(19), which were shown to be highly effective in protecting STEC-infected piglets (17,20,21). Other investigators have also developed Stx-neutralizing chimeric (47) or humanized (48,49) MAbs. HuMAb 5C12, specific for Stx2, was found to be highly effective in protecting piglets 48 h after STEC infection; a dose of 0.4 mg/kg of body weight protected 80% of piglets (20).…”
Section: Discussionmentioning
confidence: 99%
“…With this in mind, we developed HuMAbs to neutralize Stx (17)(18)(19), which were shown to be highly effective in protecting STEC-infected piglets (17,20,21). Other investigators have also developed Stx-neutralizing chimeric (47) or humanized (48,49) MAbs. HuMAb 5C12, specific for Stx2, was found to be highly effective in protecting piglets 48 h after STEC infection; a dose of 0.4 mg/kg of body weight protected 80% of piglets (20).…”
Section: Discussionmentioning
confidence: 99%
“…However, our research group is one of several that investigate passive immunization strategies to neutralize the Stxs associated with STEC infections (3,4,10,13,19,20). Our passive immunization strategy is based on murine monoclonal antibodies (MAbs) developed in this laboratory that specifi-cally bind to and neutralize Stx/Stx1 or Stx2 (21,28).…”
mentioning
confidence: 99%
“…Additionally, a third MAb (2H3) that recognizes StxB1, but not StxB1d, has been described, and residue 55 may play a role in that difference as well (3). Finally, another MAb, VTm1.1 (later humanized and called TMA-15), recognizes StxB2 and neutralizes Stx2 (12,22) but fails to recognize StxB2 when the 56th amino acid is mutated (E56H). The 55th residue of StxB1 and the 56th residue of StxB2 are both located on the outside of the B monomers in approximately the same location.…”
Section: Discussionmentioning
confidence: 99%
“…Several recent vaccine candidates not described in the above-mentioned reviews include Stx1 and Stx2 genetic toxoids, a plantbased Stx2 toxoid, and a chimeric StxA2/StxB1 toxoid that elicits a neutralizing antibody response and provides protection against a lethal challenge of both Stx1 and Stx2 (25,33,34). Several groups are pursuing passive immunization strategies that utilize humanized or human monoclonal antibodies (MAb) that neutralize one or more Stxs (6,7,12,18,19,35). STEC may produce one or more types of Stxs.…”
mentioning
confidence: 99%