Viscoelasticity reprograms T cell metabolism for TCR-T cell manufacturing and therapy

However, the ex vivo generation of metabolically fit, durable T cells capable of sustained function in the immunosuppressive solid tumor microenvironment remains a major bottleneck. While dendritic cell–based antigen presentation can provide physiological activation signals, its clinical translation is limited by donor variability, poor scalability, uncontrolled paracrine signaling, and the risk of T cell exhaustion.

Here we develop synthetic viscoelastic activating cells (SynVAC)—a class of artificial antigen-presenting cells (aAPCs) whose stress-relaxation kinetics are independently and precisely tuned while maintaining constant stiffness and defined densities of peptide–major histocompatibility complex (pMHC) and co-stimulatory ligands. SynVAC-pMHC offers a well-defined and scalable platform that outperforms monocyte-derived dendritic cells (moDCs) to enrich antigen-specific CD8+ T cells.