Microfluidic Chips: Emerging Technologies for Adoptive Cell Immunotherapy

Tian, Yishen; Hu, Rong; Du, Guangshi; Xu, Na

doi:10.3390/mi14040877

Cited by 7 publications

(1 citation statement)

References 59 publications

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“…Droplet microfluidics, as an important branch in microfluidic chip research, has a wide range of applications in biomedicine [22,23]. Unlike traditional two-dimensional cell expansion techniques for planar cultures, three-dimensional cell expansion in droplets mimics the true heterogeneity and microenvironment of the tissue [24,25]. The unique properties of droplet microfluidics make it an ideal platform for exploring techniques for low cell differentiation and rapid proliferation [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic-based preparation of artificial antigen-presenting gel droplets for integrated and minimalistic adoptive cell therapy strategies

Tian,

Chen,

et al. 2024

Biofabrication

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Adoptive T-cell transfer for cancer therapy is limited by the inefficiency of in vitro T-cell expansion and the ability of in vivo T-cells to infiltrate tumors. The construction of multifunctional artificial antigen-presenting cells is a promising but challenging approach to achieve this goal. In this study, a multifunctional artificial antigen-presenting gel droplet (AAPGD) was designed. Its surface provides regulated T-cell receptor stimulation and co-stimulation signals and is capable of slow release of mitogenic cytokines and collagen mimetic peptide (CMP). The highly uniform AAPGD are generated by a facile method based on standard droplet microﬂuidic devices. The results of the study indicate that, T-cell proliferated in vitro utilizing AAPGD have a fast rate and high activity. AAPGD increased the proportion of in vitro proliferating T cells low differentiation and specificity. The starting number of AAPGDs and the quality ratio of T-cell receptor-stimulated and co-stimulated signals on the surface have a large impact on the rapid proliferation of low-differentiated T cells in vitro. During reinfusion therapy, AAPGD also enhanced T-cell infiltration into the tumor site. In experiments using AAPGD for adoptive T cell therapy in melanoma mice, tumor growth was inhibited, eliciting a potent cytotoxic T-lymphocyte immune response and improving mouse survival. In conclusion, AAPGD promotes rapid low-differentiation proliferation of T cells in vitro and enhances T cell infiltration of tumors in vivo. It simplifies the preparation steps of ACT therapy, improves the therapeutic effect, and provides a new pathway for overdosing T cells to treat solid tumors.

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