Humanization of a mouse neutralizing monoclonal antibody against tumor necrosis factor-α (TNF-α)
1999
An anti-human tumor necrosis factor-α (TNF-α) monoclonal antibody, designated as 3B10, inhibits the biological activity of human TNF-α. In the present study, we constructed humanized version of the antibody by grafting its complementarity-determining regions (CDRs) onto a human antibody, HBS-1. Using a molecular model of mouse 3B10, framework residues affecting the CDR conformation were identified. Thus, these residues were also introduced into the framework together with the CDRs in a stepwise manner, depending on the degree of the possible importance of the residues. As a result, one humanized version (h3B10-9) which possesses nine mouse framework residues showed the same binding activity as that of the chimeric version. This humanized anti-TNF-α antibody is expected to be less immunogenic and thus more suitable for possible clinical use.
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