Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion
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 enric...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0639 |
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| Summary: | 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. |
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| ISSN: | 2639-5274 |