We show that by combining IL-2 secretion and viability assays, our screening platform accurately identifies multiple members of active compound classes and differentiates immunomodulatory or toxic activity for T cells.

The incorporation of immune function assays into structure-activity relationship (SAR) studies can provide valuable guidance for drug development. In this high-throughput screen (HTS), we focus on the health and function of primary human T cells through utilization of an AlphaLISA IL-2 assay for IL-2 secretion and CellTiter-Glo^® assay for cell survival and proliferation.

Incorporation of liquid handling automation allows for miniaturization of this assay to the 384-well format with improved throughput and reduction in material costs. Up to 28 × 10-point dose curves can be performed per 384-well plate in singlicate with replicates produced across multiple plates or 9 × 10-point dose curves performed in triplicate on a single 384-well plate. Assays can be regulated for batch-to-batch consistency and data turn around reduced to 48 hours from drug treatment.

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To cite this poster: Foss, M. and Hoffman, D. Immunomodulation of primary human T cell activation using high-throughput screen of FDA-approved small molecule drugs. Poster presented at: 18^th Annual Drug Discovery Chemistry Conference; April 10-13, 2023.