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Reversible control of CAR T cells through PROTAC compound
Abstract No. : 106

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Engineered T cell therapy (e.g., CAR/TCR-T)
Proteolysis-targeting chimera (PROTAC) is an innovative strategy for selectively degrading target proteins. In this study, we demonstrate that a PROTAC compound, specifically degrades a degron-tagged chimeric antigen receptor (CAR-degron). In vitro, PROTAC reversibly modulates the activity of CAR-degron T cells through targeted CAR degradation. In preclinical models, CAR-degron T cells exhibit potent antitumor activity comparable to conventional CAR T cells, and PROTAC effectively regulates the activity of CAR-degron T cells. Together, these results suggest that the PROTAC-degron-tagged-CAR system can serve as an efficient tagging platform for targeted CAR protein degradation, thereby enabling successful and reversible control of CAR T cell activity in patients.
#CAR T cell therapy
#Targeted protein degradation (TPD)
#Controllable CAR T
#Safety switch
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