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. Author manuscript; available in PMC: 2022 Mar 8.
Published in final edited form as: Nat Rev Clin Oncol. 2021 Mar 2;18(7):401–417. doi: 10.1038/s41571-021-00479-z

Fig. 4 |. Genetically engineered cell therapies regulated by targeted protein degraders.

Fig. 4 |

The figure outlines an example of the use of lenalidomide as a molecular ‘switch’ to dynamically control the activity of chimeric antigen receptor (CAR) cells. Specifically, a lenalidomide-responsive ‘degron’ moiety (for example, a zinc finger domain derived from IKZF3 can be incorporated in the CAR construct. These degradable constructs can then be used to generate CAR T cells that can be rapidly and reversibly turned ‘off’ through lenalidomide treatment in order to tune CAR signalling or mitigate toxicities associated with T cell hyperactivation. HaloTags or dTags, which also confer the ability to control expression of the engineered protein using small-molecule degraders, could be substituted for the lenalidomide-responsive degron.