Remote control of therapeutic T cells through a small molecule–gated chimeric receptor

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…

• HH
  Howard Hughes Medical Institute
• JC
  Jane Coffin Childs Memorial Fund for Medical Research

  Award: A121505
• NI
  National Institutes of Health

  Awards: P50 GM081879, F32 GM101782, R01 CA196277, R01 GM055040, PN2 EY016546