A Cryogel-Based Dendritic Cell Vaccine for Post-Surgical Breast Cancer Immunotherapy

Triple-negative breast cancer (TNBC) is an aggressive malignancy with high mortality and limited treatment options. While surgical resection removes the primary tumor, it often fails to prevent recurrence or metastasis, and despite the promise of immunotherapy, the response to immune checkpoint blockade remains poor. Here, we develop a cryogel-based dendritic cell (DC) vaccine that integrates gold nanodot-lipopolysaccharide (AuLPS)-loaded DCs, doxorubicin (Dox), and a PD-1 immune checkpoint blockade, effectively enhancing anti-tumor immunity in the post-surgical setting. The AuLPS nanoparticles (NPs) stabilize LPS assembly, optimizing Th1 adjuvant activity, thereby improving DC vaccine efficacy while minimizing adverse effects. The cryogel enables the sustained localized release of therapeutic agents at the surgical site, preserving DC viability, migration, and functionality within the tumor microenvironment. This strategy enhances DC activation and potentiates robust T-cell activation in both tumor-draining lymph nodes and tumor beds, leading to durable anti-tumor immunity. When administered at the post-surgical site in an orthotopic TNBC model, the aPD-1+Dox+AuLPS@DC cryogel vaccine significantly delays tumor recurrence, reduces distant metastases, and prolongs survival. These findings highlight cryogel-based DC vaccines as a promising post-surgical immunotherapy to overcome the limited response to immune checkpoint blockade and improve TNBC outcomes. Overall design: Comparative gene expression profiling analysis of RNA-seq data for murine TNBC tumors with or without treatment of DOX and AuNP treated BMDC co-loaded cryogel