Pharmacological screening to identify potential regulators of antigen presentation by dendritic cells

High-throughput screening (HTS) is a cornerstone of modern drug discovery and particularly important for the development of novel anticancer therapeutics as it allows to identify agents with specific biological activities among a large number of chemical compounds. So far, most anticancer HTS approaches focused either on specifically targeting pathways critical for tumor development or on identifying drugs capable of increasing the immunogenicity of cancer cells, thus directly decreasing tumor cell viability or rendering them detectable to the immune system, respectively. Here, we employ an in vitro antigen presentation system for HTS with the purpose to identify agents that exhibit immunostimulatory potential in the context of dendritic cell (DC)-mediated antigen presentation. To this aim DCs derived from immortalized precursors are treated with an array of compounds and are then confronted with the model antigen ovalbumin (OVA). Coculture of these DCs with T-cell hybridoma cells expressing an OVA-specific T cell receptor (TCR) that triggers the secretion of IL-2 then allows the ELISA-quantifiable assessment of antigen presentation. Altogether, this system can be used to identify immunomodulatory drugs that affect the intricate crosstalk between innate and adaptive immunity.