Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies
Menée à l'aide d'un dispositif microfluidique, d'un modèle murin de lymphome humain et de xénogreffes de cancer de l'ovaire, cette étude met en évidence l'intérêt, pour augmenter l'efficacité de traitements anticancéreux, de cellules synthétiques visco-élastiques présentant les propriétés mécaniques des cellules natives présentatrices de l'antigène
The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8+ T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.
Nature Biomedical Engineering , résumé, 2024