Cell Rep: a new screening method can identify potential anticancer compounds that can wake up T cells

December 6, 2019 / BIOON / -- Scripps Research Scientists have developed a new compound to treat cancer by restoring the antitumor activity of T cells The results were published in cell reports Tumors often lead to T cell dysfunction or "burnout." New methods have found medicinal compounds that can restore the function of these T cells, making cancer "sensitive" again Using rapid screening of more than 12000 drug compounds, scientists found 19 drugs that can wake up T cells (image source: www Pixabay Com), the author of the article, Dr oldstone said: "this new screening method should be particularly useful, because we can not only use it to identify compounds that can restore the functions of T cells, but also quickly analyze these T cells to determine how these compounds work on them." Immunotherapy is one of the most powerful anticancer drugs nowadays, which can block the signal of PD-1 or similar receptor to restore the anticancer response of T cells These treatments have saved many cancer patients who looked incurable in the past But because these drugs are usually effective only for several cancers, including melanoma, and less for others, scientists suspect that cancer often hijacks multiple suppressive T-cell pathways This suggests that the combination of immunotherapies for different molecular pathways may be more effective than current therapies The new screening system is designed to allow scientists to quickly find such drugs - in which case their pharmacologically active small molecule compounds may be better or more effective than currently available antibody immunotherapies that can be injected The system uses lcmv-13 to infect "depleted" T cells and screen the ability of test compounds to "wake up" these cells again One advantage of the new screening system is that it is specific and highly automated As a result, thousands of combinations can be tested in a few days, Oldstone and colleagues applied the new screening system to drug reuse libraries containing more than 12000 compounds that have been FDA approved or have passed potential drug testing Further, they found 19 hit compounds that effectively restore the activity of tired T cells One of these compounds, eugenol butanediol ester, is a plant derived molecule that can be used to treat actinic keratosis, a precancerous skin disease The researchers found that eugenol mesylate restores the function of T cells by activating a signaling enzyme called protein kinase C, the active pathway of the compound Oldstone points out that the new screening method is flexible enough to find compounds that have other effects on T cells, such as reducing T cell activity to treat autoimmune diseases Information sources: new screening method identifications potential anticancer complexes that reawaken T cells original sources: Brett s Marro, Jaroslav Zak, Reza Beheshti zavareh, John R teijaro, Luke L lairson, Michael B.A oldstone Discovery of small molecules for the reversal of T cell evolution Cell reports, 2019; 29 (10): 3293 DOI: 10.1016/j.celrep.2019.10.119