Mesoporous silica (MPS) vaccine to enhance anti-tumor immunity
Aileen Li1,2,, Maxence Dellacherie1,2, Omar Ali2, Beverly Lu2, Ting-Yu Shih1,2, and David J Mooney1,2*
1School of Engineering and Applied Sciences, Harvard University; 2Wyss Institute, Harvard University
Biomaterials have shown substantial potential to integrate synergistically with current cancer vaccine strategies and enhance their effectiveness. We recently developed an injectable biomaterial vaccine via spontaneous assembly of mesoporous silica (MPS) microparticles into a 3D scaffold in vivo. When formulated with GM-CSF and CpG, the MPS vaccine modulates host dendritic cell (DC) activation and trafficking. Here we demonstrate that a single injection of the MPS vaccine induced persistent germinal center activity for over 30 days. Consequently, when immunized with a small linear Her2/neu peptide within the Trastuzumab binding domain, the MPS vaccine elicited over 20 fold higher IgG1 and IgG2a antibody titer compared to a bolus vaccine, and the antibody exhibited reactivity on the native Her2 structure on breast cancer cells. To further enhance CTL responses against tumor antigens, we co-presented the antigen with polyethylenimine (PEI) in the MPS vaccine. PEI increased antigen cross-presentation in murine DCs, and TNF-a and IL-6 production in both murine and human DCs in vitro. Compared to the MPS vaccine, the MPS-PEI vaccine enhanced activated DCs in the vaccine and the vaccine dLN by ~2 fold. Systemically, the MPS-PEI vaccine induced ~2.5 fold higher IFN-y producing antigen specific circulating CD8+ T cells compared to the MPS vaccine. Impressively, using a HPV-E7 expressing tumor model, we demonstrated that a single injection of the MPS-PEI vaccine completely eradicated large established tumors in over 80% of mice. Finally, when immunized with a pool of recently sequenced B16 melanoma neoantigen peptides, the MPS-PEI vaccine induced therapeutic tumor growth control and synergy with anti-CTLA4 therapy. These findings suggest that the MPS vaccine may serve as a facile multifunctional and multi-epitope platform to modulate host immune cell function and augment personalized anti-tumor immunity.
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