CAR signaling domain cut to 45 amino acids: Canelé's agent-designed receptor beats BBζ on surface expression
Canelé used an AI-agent-orchestrated rational design loop to refactor the CAR intracellular signaling domain, compressing the second-generation BBζ domain into a 54-amino-acid design called Stoat and then a 45-amino-acid variant, Happy Stoat. At the same mRNA dose, Happy Stoat puts more CAR on the T-cell surface than both BBζ and Stoat and releases more cytokine. Across five donors, Happy Stoat matched BBζ's B-cell depletion at lower mRNA doses.