Researchers from Harvard’s Wyss Institute, Harvard SEAS, and Genentech have made a breakthrough in enhancing and prolonging lymph node (LN) expansion to potentially improve vaccine efficacy against tumors. Lymph nodes, which expand and contract in response to immune triggers like infections and vaccines, play a critical role in mounting immune responses. Traditionally, LN expansion occurs temporarily after vaccination. However, these researchers engineered a biomaterial-based vaccine that sustains LN expansion and increases the presence of immune cells essential for a robust response against melanoma in mice.
The vaccine uses mesoporous silica (MPS) rods to release immune-stimulating agents, creating a scaffold near tumors that attracts and reprograms immune cells, particularly antigen-presenting cells. Monitoring LN changes over 100 days with high-frequency ultrasound and nanoindentation tools, researchers observed a peak in LN volume expansion, which then stabilized at a significantly larger size than those induced by conventional vaccines. The expanded LNs showed higher populations of immune cells, such as monocytes, dendritic cells, T cells, and B cells, which coordinated a strong immune response over a prolonged period.
The team explored the impact of LN expansion on immune response by targeting various immune cells, identifying specific monocyte populations that could promote LN growth. They discovered that priming LNs with MPS-vaccine scaffolds before administering a traditional vaccine significantly boosted the anti-tumor response in a melanoma model, leading to extended survival in treated mice. The researchers suggest this “LN priming” approach may open new avenues for vaccine and immunotherapy design by leveraging biomaterials to influence immune mechanics.
This work exemplifies the importance of physical and structural changes in enhancing immune function, providing new insights into the role of LN mechanics in immune responses and opening doors for further vaccine and immunotherapy innovations. The study is published in Nature Biomedical Engineering.
