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Synthetic Viscoelastic Activating Cells for T Cell Engineering and Cancer Therapy

ABSTRACT: Immunotherapy shows promise in cancer treatment, but its effectiveness and durability remain limited, and improved technology for engineering immune cells is necessary. Here we develop a scalable platform that creates synthetic viscoelastic activating cells (SynVACs) with programmable mechanical and chemical properties. We demonstrate that the viscoelastic nature of SynVACs significantly impacts T cell functionality. Compared to rigid or elastic microspheres, SynVACs greatly enhance human T cell expansion, achieving approximately 90% chimeric antigen receptor (CAR) transduction efficiency. Additionally, SynVACs promote CD8+ T cell generation while suppressing regulatory T cell formation, resulting in enhanced tumor killing capability. Notably, expanding CAR-T cells with SynVACs leads to a ten-fold increase in T memory stem cells (TMSCs). These engineered CAR-T cells exhibit superior efficacy in eliminating tumor cells in a human lymphoma and ovarian xenograft mouse model, persisting in vivo for longer time period. These findings underscore the crucial role of mechanical signals in T cell engineering and highlight SynVACs' potential in CAR-T therapy and imunoengineering applications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242531 | GEO | 2023/09/12

REPOSITORIES: GEO

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