基于微流控技术制备人工抗原呈递凝胶微滴用于集成化和极简式过继细胞治疗策略

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 (TCR) stimulation and co-stimulation signals and is capable of slow release of mitogenic cytokines and collagen mimetic peptide. 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 TCR-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 adoptive cell therapy, improves the therapeutic effect, and provides a new pathway for overdosing T cells to treat solid tumors.