Synthetic transcription factors designed by domain recombination enhance CAR T cell antitumor function

A novel domain-recombination strategy called DESynR generates synthetic AP-1 transcription factors that reprogram CAR T cells into non-natural, therapeutically optimized states with superior antitumor function compared to their natural counterparts. By systematically recombining domains across an entire protein family rather than relying on evolutionarily shaped sequences, the researchers created transcription factors that outperform all tested natural AP-1 factors in driving antitumor immunity. The work, published in Cell, opens a new design space for engineering immune cell therapies beyond the constraints of natural protein evolution.