Dextran-based T-cell expansion nanoparticles for manufacturing CAR T cells with augmented efficacy
- Tao Zheng
- Keerthana Ramanathan
- Maria Ormhøj
- Mikkel Rasmus Hansen
- Hólmfridur Rósa Halldórsdóttir
- Hanxi Li
- Kamilla Kjærgaard Munk
- Carlos Rodriguez-Pardo
- Rasmus Ulslev Wegener Friis
- Islam Seder
- Peter M. H. Heegaard
- Klaus Qvortrup
- Hinrich Abken
- Yi Sun
- Sine Reker Hadrup
2026-01-20
Adoptive T cell therapy 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. “T-Expand” is developed for T cell activation and expansion, comprising dextran-based nanoparticles conjugated with anti-CD3 and anti-CD28 antibodies. The nanoparticles trigger robust polyclonal expansion of human T cells with efficiency in the range of commercial microbeads (Dynabeads™). Engineered in the presence of T-Expand, CD19 CAR T cells display enhanced proliferative capacity, cytotoxicity and persistence in vitro, and furthermore, exhibit potent 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 TM . As a biocompatible T cell expansion platform, T-Expand simplifies the manufacturing process while enhancing T cell persistence and functionality, and thereby holds promise for increasing clinical efficacy of CAR T cell therapy.