Flow cytometry and receptor occupancy in immune-oncology.

Alessandra Audia, Gregory Bannish, Rachel Bunting, Chelsea Riveley

Expert opinion on biological therapy 2022 Jan

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Immunotherapies are focused on strategies that alter immune responses, using antibodies that binds to receptors on different immune cell subsets and either activate or suppress their functions depending on the immune response being targeted. Hence, the necessity of developing assays that assess the functional and biological effect of a therapeutic on its target. When incorporated into high-parameter flow cytometry panels, receptor occupancy assay can simultaneously evaluate receptor expression and drug occupancy on defined cell subsets, which can provide information related to functional effects, and safety. This review focuses on the importance of developing, optimizing, and validating a robust Receptor Occupancy Assay (ROA) to improve dose selection, pharmacology monitoring and safety mainly in clinical settings. The designing of an ROA can be challenging and can lead to exaggerated pharmacology if not accurately developed, optimized, and validated. However, improvements in our understanding of epitopes, binding, affinities, and pharmacological effects may lead to improved antibody drug targeting and receptor evaluation.

Citation

Alessandra Audia, Gregory Bannish, Rachel Bunting, Chelsea Riveley. Flow cytometry and receptor occupancy in immune-oncology. Expert opinion on biological therapy. 2022 Jan;22(1):87-94