Immunotherapy for Tumor Metastasis by Artificial Antigen-Presenting Cells via Targeted Microenvironment Regulation and T-Cell Activation

Effective expansion of T-cells without ex vivo stimulation and maintenance of their antitumor functions in the complex tumor microenvironment (TME) are still daunting challenges in T-cell-based immunotherapy. Here, we developed biomimetic artificial antigenpresenting cells (aAPCs), ultrathin MnOx nanoparticles (NPs) functionalized with T-cell activators (anti-CD3/CD28 mAbs, CD), and tumor cell membranes (CMs) for enhanced lung metastasis immunotherapy. The aAPCs, termed CD-MnOx@CM, not only efficiently enhanced the expansion and activation of intratumoral CD8(+) cytotoxic T-cells and dendritic cells after homing to homotypic metastatic tumors but also regulated the TME to facilitate T-cell survival through catalyzing the decomposition of intratumoral H2O2 into O-2. Consequently, the aAPCs significantly inhibited the development of lung metastatic nodules and extended the survival of a B16-F10 melanoma metastasis model, while minimizing adverse events. Our work represents a new biomaterial strategy of inhibiting tumor metastasis through targeted TME regulation and in situ T-cell-based immunotherapy.

Automated summary

In this study, biomimetic artificial antigen-presenting cells (aAPCs) were developed using ultrathin MnOx nanoparticles functionalized with T-cell activators and tumor cell membranes to enhance lung metastasis immunotherapy. These aAPCs efficiently expanded and activated intratumoral CD8(+) T cells and dendritic cells, while regulating the tumor microenvironment (TME) to facilitate T-cell survival.