3D-Printed Dendritic Cell Vaccines for Post-Surgery Cancer Immunotherapy

Dendritic cell (DC) vaccines have shown promising effects in cancer management, while low cell activity and low migration rate to lymph nodes limit their clinical application. Here, this work reports a bioink DC vaccine, synthesized by 3D printing methacryloyl gelatin to encapsulate DCs and tumor cellular vesicles overexpressing programmed cell death protein 1 (PD1-CVs), for cancer immunotherapy. Compared with a traditional hydrogel, the porous 3D scaffold significantly improves the viability of DCs from similar to 16% to similar to 70% after 7 days of cell culture and increases the proportion of released DCs from the scaffold into lymph nodes by about fourfold. The PD1-CVs stimulate DC maturation and block PD ligand-1 (PD-L1) in mature DCs and tumor cells, synergistically boosting DC-mediated antitumor immunity. In breast tumor mouse models, this personalized 3D DC vaccine developed for site-specific filling after tumor resection significantly suppress tumor recurrence and extend median survival time to 45 days. This 3D printed vaccine offers a simple, safe, and robust strategy for enhanced cell-based cancer immunotherapy. DC bioink vaccine is 3D printed as a porous scaffold following the direct physical mixing of DCs, PD1-CVs and hydrogel. PD1-CVs function as "immunomodulators" for DCs, while hydrogel scaffolds serve to store and sustainably release DCs, synergistically enhancing the anti-tumor efficacy of DCs. image