动态肿瘤免疫芯片用于外周血来源的肿瘤反应性 T 细胞扩增

Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner.

Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel. Then, T cells were infused and fully contacted with these tumor spheroids under biomimetic flow conditions provided by herringbone-patterned microgrooves arrays.

We found that the tamed tumor-reactive T cells could be fully activated and a rapid clonal proliferation was realized during the cultivation.

In addition, these tumor-reactive T cells exhibited a specific and powerful tumor-killing capability in vitro.

Thus, the suggested dynamic microfluidic chips with staged structure-transformable properties realize both the producible formation of tumor spheroids and the recapitulation of tumor-immune crosstalk to expand tumor-reactive T cells. These features indicate that the dynamic and reproducible tumor immunology-on-a-chip has potential in the preparation of therapeutic T cell products for clinical cancer immunotherapy.