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Remote control of therapeutic T cells through a small molecule–gated chimeric receptor
Ist Teil von
Science (American Association for the Advancement of Science), 2015-10, Vol.350 (6258), p.293-293
Ort / Verlag
United States: American Association for the Advancement of Science
Erscheinungsjahr
2015
Link zum Volltext
Quelle
American Association for the Advancement of Science
Beschreibungen/Notizen
There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control.