In situ generation of dendritic cell vaccines in 3D printing scaffolds for cancer post-surgical therapy

Abstract

Dendritic cell (DC) vaccines have shown great promise in cancer management, while complex ex vivo cell culture limits their clinical applications. Here, we report an in situ-generated scaffold DC vaccine, comprising a simple 3D-printed gelatin methacryloyl, bone marrow mononuclear cells (BM-MNCs), tumor lysates and stimulating factors. Stimulating factors in this vaccine effectively initiated in situ differentiation of BM-MNCs into DCs, while personalized tumor lysates stimulated the maturation of differentiated DCs and enhanced their lymph node migration efficiency, thereby synergistically strengthening their antitumor effects. Moreover, the 3D hydrogel scaffold serves as an in situ cell culture matrix, promoting the long-term viability of encapsulated cells and providing a conducive environment for BM-MNC differentiation and DC maturation within the surgical bed. In a prostate cancer post-surgical mouse model, the vaccine significantly inhibited tumor growth, suppressed tumor metastasis and extended median survival of animals to 55 days. This in situ-generated DC vaccine bypasses ex vivo cell culture, offering a simple, safe and robust strategy to elicit antitumor immunity for cancer treatment.