Figure 4

Model-predicted reduction in cell proliferation in response to antibody treatment indicated that IGF1R-blocking antibodies will be more effective than IGF1-neutralizing antibodies. A range of antibody dissociation constants (K _d , 0.1-10 nM) were used to simulate the effect of high to low binding affinity. The effects of the antibody in the presence of three different IGFBP concentrations at A, low (0.1 nM) or B, high (2.5 nM) IGF1 level were determined using the steady-state model. Model results indicated that an antibody that blocks IGF1R would more strongly decrease the steady-state concentration of IGF1-IGF1R complexes and consequently, inhibit IGF1-induced cell proliferation, than an antibody that binds and neutralizes IGF1.