Neutralization of activity of effector protein by monoclonal antibody: formulation of antibody dose-dependence of neutralization for an equilibrium system of antibody, effector, and its cellular receptor.

Binding of an antibody to an effector protein will not necessarily inactivate it totally. In order to incorporate this into mathematical expressions of neutralization reaction between a monoclonal antibody and an effector which acts on cells through receptor binding, a static equilibrium system was considered that consists of effector, receptor and antibody, allowing formation of the ternary complex. A formula was derived for the antibody dose-dependence of neutralization, which was qualitatively similar to that found experimentally for monoclonal antibodies to interferon. According to the formula, the extent of neutralization, N, will approach a saturation value N infinity at high antibody concentrations, instead of increasing indefinitely, as is the case with conventional antibodies; the value N infinity is determined by the degree of reduction, upon antibody binding, of the effector's affinity to the receptor (and/or by the ability of antibody to inhibit the effector action subsequent to receptor binding). On the other hand, experimental data in the region of small N's will allow one to estimate the effector-antibody association constant.