A humanized antibody that binds to the interleukin 2 receptor.

TLDR

The anti‑Tac monoclonal antibody binds the p55 chain of the human interleukin‑2 receptor and blocks T‑cell proliferation, but its murine origin elicits an immune response that limits its therapeutic use. To overcome this limitation, the authors engineered a humanized antibody by grafting the anti‑Tac complementarity‑determining regions onto human framework and constant regions. The human framework was selected for maximal sequence homology, and a computational model identified and retained key murine residues outside the CDRs that likely interact with the antigen or CDRs. The resulting humanized anti‑Tac antibody binds p55 with a 3 × 10^9 M^−1 affinity, roughly one‑third that of the original murine antibody.

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.