Refactored intracellular domains enhance CAR expression and function

Iterative AI-guided refactoring produced KRGR-{zeta}1-40, a 45–amino-acid CAR intracellular domain that is less than a third the length of the clinical BB{zeta} ICD.

• Why it matters: CAR intracellular domains must efficiently link antigen recognition to T-cell activation, but compact designs that preserve function are challenging to engineer.
• What they did: Using AI agents over three design-and-measurement rounds, the team compared KRGR-{zeta}1-40 with BB{zeta} for CAR surface expression, antigen-driven IFN-{gamma} release, and killing after transient mRNA or shared-dose expression, plus lentiviral and lipid-nanoparticle delivery.
• The result: KRGR-{zeta}1-40 increased CAR surface expression and antigen-driven IFN-{gamma} release without antigen-independent IFN-{gamma}, extended expression and target-cell killing after mRNA delivery, supported four CARs from one mRNA dose, and enhanced B-cell depletion after lentiviral and lipid-nanoparticle delivery.

AI summary of the abstract · may contain errors · not medical advice · read the paper.