Zheng, T.; Ramanathan, K.; Ormhoj, M.; Hansen, M. R.; Halldorsdottir, H. R.; Li, H.; Munk, K. K.; Rodriguez-Pardo, C.; Friis, R. U. W.; Islam, S. F.; Heegaard, P. M. H.; Qvortrup, K.; Abken, H.; Sun, Y.; Hardup, S. R.

Adoptive T cell therapy (ACT) using chimeric antigen receptor (CAR) engineered T cells is currently being explored in multiple cancer types beyond leukemia/lymphoma. A key step in CAR-T cell manufacturing is the activation and expansion of T cells, which facilitates viral transduction, however, may hamper T cell fitness and reduce in vivo persistence. We developed T-Expand for T cell activation and expansion, comprising dextran-based nanoparticles (NPs) conjugated with anti-CD3 and anti-CD28 antibodies. The NPs triggered robust polyclonal expansion of human T cells with efficiency in the range of commercial microbeads (Dynabeads). Engineered in presence of T-Expand, CD19 CAR T cells exhibited enhanced proliferative capacity, cytotoxicity and persistence in vitro, and furthermore, showed superior anti-lymphoma activity in mouse models resulting in complete tumor clearance at one fourth of the CAR T cell dose. Importantly, T-Expand is biocompatible with no observed toxicity, circumventing removal steps after T cell expansion compared to Dynabeads. As a biocompatible T cell expansion platform, T-Expand simplifies the manufacturing process while enhancing T cell persistence and functionality, thereby holding promise for increasing clinical efficacy of CAR T cell therapy.