Monoclonal antibody tissue cross-reactivity assay

Tissue cross-reactivity studies, although burdensome, provide a rational in vitro assay to determine the range and intensity of distribution of potential epitopes reactive with a monoclonal antibody test article prior to its administration to humans. In addition, cross-reactivity studies provide a useful tool to identify animal species for safety assessment. The cross-reactivity profiles of different species can be compared to the profiles obtained in human tissues. The predictive value of the assay lies in incorporating the characteristics of the monoclonal antibody (isotype, subtype, and other molecular modifications) with the biological activity of the molecule itself, and the potential in vivo distribution of it. 

The evaluations to determine relevant species for toxicity evaluation include various receptor binding assays and tissue cross-reactivity assessments, the later being routinely performed for monoclonal antibody based products (see Chapters 10 and 26). Species specificity can be determined using properly controlled in vitro cell-based response assays, cloning of receptors and ligands to determine compatibility, receptor-based response assays, immunoassays, genomic-based assays, and traditional biochemical-based assays as well as in vivo assessments with validated endpoints and markers for specificity. 

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