HUMANIZATION OF A MOUSE ANTI-HUMAN IGE ANTIBODY - A POTENTIAL THERAPEUTIC FOR IGE-MEDIATED ALLERGIES

Mouse mAb TES-C21(C21) recognizes an epitope on human IgE and, therefo re, has potential as a therapeutic agent in patients with IgE-mediated allergies such as hay fever, food and drug allergies and extrinsic as thma. The clinical usefulness of mouse antibodies is limited, however, due to their immunogenicity in humans. Mouse C21 antibody was humaniz ed by complementarity determining region (CDR) grafting with the aim o f developing an effective and safe therapeutic for the treatment of Ig E-mediated allergies. The CDR-grafted, or reshaped human, C21 variable regions were carefully designed using a specially constructed molecul ar model of the mouse C21 variable regions. A key step in the design o f reshaped human variable regions is the selection of the human framew ork regions (FRs) to serve as the backbones of the reshaped human vari able regions. Two approaches to the selection of human FRs were tested : (i) selection from human consensus sequences and (ii) selection from individual human antibodies. The reshaped human and mouse C21 antibod ies were tested and compared using a biosensor to measure the kinetics of binding to human IgE. Surprisingly, a few of the reshaped human C2 1 antibodies exhibited patterns of binding and affinities that were es sentially identical to those of mouse C21 antibody.