NOVEL lymph-node-inspired hydrogels enhance CAR T cell activation and proliferation by 50%, offering a more efficient and cost-effective method for producing this cutting-edge cancer immunotherapy, according to a study published in ACS Applied Materials & Interfaces.
CAR T cell therapy, which modifies a patient’s immune cells to target cancer, has revolutionised treatment for certain blood cancers but faces challenges in manufacturing efficiency and cost. Traditional methods rely on suspension cultures, which often yield inconsistent results. Researchers from the Institute of Materials Science of Barcelona (ICMAB-CSIC) and IDIBAPS-Hospital Clínic developed biomimetic hydrogels mimicking lymph node structures—where T cells naturally activate. These poly(ethylene glycol)-heparin hydrogels feature interconnected pores (120 μm) and tissue-like stiffness (3.1 kPa), replicating mechanical and biochemical cues critical for T cell function.
Lab tests demonstrated a 50% increase in CAR-positive cells and a doubling of the replication index compared to conventional methods. Theoretical simulations revealed heparin in the hydrogels electrostatically binds to viral vectors used in gene delivery, enhancing CAR gene transfer efficiency. This interaction increased contact between viral particles and T cells, improving transduction without altering the vectors themselves. The hydrogels also reduced reliance on costly cytokines, streamlining production.
These findings highlight the potential for hydrogels to standardise CAR T manufacturing, lowering costs and improving accessibility. Clinicians could soon adopt this platform to produce higher-quality therapies for solid tumours, currently a hurdle for CAR T efficacy. Future steps include scaling production and clinical trials to validate long-term safety and effectiveness. Integrating such biomaterials into existing workflows could transform adoptive cell therapies, broadening their application in oncology.
Reference
Miquel Castellote-Borrell et al, Lymph-Node Inspired Hydrogels Enhance CAR Expression and Proliferation of CAR T Cells, ACS Applied Materials & Interfaces (2025). DOI: 10.1021/acsami.4c19942.
