A humanized antibody that binds to the interleukin 2 receptor.

Abstract:

:The anti-Tac monoclonal antibody is known to bind to the p55 chain of the human interleukin 2 receptor and to inhibit proliferation of T cells by blocking interleukin 2 binding. However, use of anti-Tac as an immunosuppressant drug would be impaired by the human immune response against this murine antibody. We have therefore constructed a "humanized" antibody by combining the complementarity-determining regions (CDRs) of the anti-Tac antibody with human framework and constant regions. The human framework regions were chosen to maximize homology with the anti-Tac antibody sequence. In addition, a computer model of murine anti-Tac was used to identify several amino acids which, while outside the CDRs, are likely to interact with the CDRs or antigen. These mouse amino acids were also retained in the humanized antibody. The humanized anti-Tac antibody has an affinity for p55 of 3 x 10(9) M-1, about 1/3 that of murine anti-Tac.

authors

Queen C,Schneider WP,Selick HE,Payne PW,Landolfi NF,Duncan JF,Avdalovic NM,Levitt M,Junghans RP,Waldmann TA

doi

10.1073/pnas.86.24.10029

subject

Has Abstract

pub_date

1989-12-01 00:00:00

pages

10029-33

issue

24

eissn

0027-8424

issn

1091-6490

journal_volume

86

pub_type

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