Preclinical immunogenicity testing for recombinant therapeutic proteins.

The assessment of the immunogenicity of recombinant therapeutic proteins (RTPs) has received more attention in the past 4 years than in the previous 20 years. The induction of clinically adverse events in RTP-treated patients and the subsequent measurement of antibodies to those RTPs has challenged the scientific community to re evaluate the methods and techniques used for determining the immunogenic potential of therapeutic proteins. One preclinical strategy for determining the relative immunogenicity of RTPs is the use of a comparative hyperimmunization technique in animals that optimizes an immunological response. This approach has utility for analyzing the immunogenic potential of different formulations as well as for potential adverse effects. The hyperimmunization model may also provide a source of antisera specific to the RTP that can be used during selection of the appropriate assay technique(s) and conditions for measuring the immune response. Solid- or liquid-phase, affinities and the frequency of washes, isotypes, and sensitivities are key parameters that have become the focus of assay development techniques. The techniques that will be discussed include enzyme-linked immunoassays, surface plasmon resonance (Biacore), and capillary electrophoresis.