Remote control of therapeutic T cells through a small molecule–gated chimeric receptor
Year: 2015
Type: article
Abstract: 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.
Source: Science
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Exploring Design Principles of Cellular Control Circuits, Synthetic immunoreceptor systems for combinatorial tumor antigen detection, Protein Recognition in Signal Transduction, G5905035499, Redesigning the T cell: Using Synthetic Biology to Engineer Therapeutic Cells, Cellular Control: Synthetic Signaling/Motility (RMI)
OpenAlex ID: W1753684754