As CAR-T cell therapy gains prominence in treating hematologic cancers, challenges remain in efficient T cell activation and maintaining long-term efficacy during ex vivo manufacturing. Conventional approaches relying on antibody-coated beads or plates fall short of recapitulating the dynamic and flexible nature of natural immunological synapses between T cells and antigen-presenting cells.
In a recently published Perspective article in Science Bulletin , researchers from the Department of Bioengineering and the Department of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles (UCLA), presented biomaterial strategies that mimic the architecture and mechanical properties of immunological synapses to optimize CAR-T cell production. The article is titled “Biomaterials Mimicking Immunological Synapses for Enhanced T Cell Activation in CAR-T Therapy.”
The authors describe two innovative platforms: (1) a graphene oxide-based antigen-presenting platform (GO-APP), which leverages flexible 2-D interfaces to enhance T cell activation, increase CAR transduction rates, and eliminate the need for exogenous IL-2; and (2) synthetic viscoelastic T-cell activating cells (SynVACs), which emulate mechanical properties of immunological synapses to promote memory T cell formation and distribution across tissues.
Looking ahead, the authors propose further engineering directions, such as dynamic ligand presentation, lateral mobility, electrochemical modulation, and redox-responsive environments, to regulate T cell activation and fate decisions more precisely.
Science Bulletin