Regulation of CAR transgene expression to design semiautonomous CAR-T.

ABSTRACT

Effective transgene expression is critical for genetically engineered cell therapy. Therefore, one of CAR-T cell therapy's critical areas of interest, both in registered products and next-generation approaches is the expression of transgenes. It turns out that various constitutive promoters used in clinical products may influence CAR-T cell antitumor effectiveness and impact the manufacturing process. Furthermore, next-generation CAR-T starts to install remotely controlled inducible promoters or even autonomous expression systems, opening new ways of priming, boosting, and increasing the safety of CAR-T. In this article, a wide range of constitutive and inducible promoters has been grouped and structured, making it possible to compare their pros and cons as well as clinical usage. Finally, logic gates based on Synthetic Notch have been elaborated, demonstrating the coupling of desired external signals with genetically engineered cellular responses.