Epitope turnover

The turnover of the epitope affects the selection of the dose and dose regimen. The dosing schedule should mimic clinical use, because the pharmacokinetics of MAbs are so variable and dose-dependent. Pragmatically, it may be difficult to administer antibodies at a high multiple of the anticipated human exposure. 

A single species may not always be sufficient for the safety evaluation of MAbs in some instances, multiple species are warranted. Transgenic models can be very useful, but it is important to have accurate information about the distribution of the epitope, its density, turnover, expression and, above all, its function in such animals. 

It is much easier to estimate the amount of MAb required to saturate a soluble epitope, if it is freely circulating, than one which is expressed only on the cell surface. However, soluble epitopes may be receptor-bound and concealed in a tissue compartment, making it difficult to estimate the levels of antibody needed for saturation. Also, turnover of the epitope may affect the selection of the dose and dose regimen. 

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