Search

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 the TLR-9 agonist 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 B cell 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 2 orders of magnitude higher IgG1 and IgG2a antibody titer compared to a traditional bolus vaccine, and the antibody exhibited immunoreactivity 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 and antigen+ DCs in the vaccine and the vaccine draining lymph node by ~2 fold. Systemically, using both OVA and a HPV-E7 peptide as antigens, 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 potent therapeutic tumor growth control and synergy with anti-CTLA4 checkpoint blockade 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 antitumor immunity. Citation Format: Aileen W. Li, Maxence O. Dellacherie, Miguel Sobral, Omr O. Ali, Jaeyun Kim, David J. Mooney. DC-recruiting biomaterial vaccine to enhance antitumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B119.

Certain chemotherapeutic drugs can elicit immunogenic death of tumor cells and enhance antitumor immune responses. Here we explore whether immunogenic chemotherapy can be utilized for the development of antigen-free cancer vaccines, by combining it with peritumorally injected biomaterial scaffolds that recruit dendritic cells (DCs) for subsequent antigen presentation and T-cell priming. Pore-forming alginate gels containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and a doxorubicin-iRGD conjugate were found to efficiently induce the apoptosis of 4T1 triple-negative breast cancer cells in vivo, while recruiting large numbers of DCs. The co-encapsulation of CpG oligodeoxynucleotides in the gel significantly enhanced the immunogenic death of 4T1 cells, increased systemic tumor-specific CD8+ T-cells and tumoral infiltration of CD8+ T-cells, repolarized tumor-associated macrophages towards an inflammatory M1-like phenotype, and resulted in significantly improved antitumor efficacy. This in situ antigen-free gel vaccine shows promise for the treatment of poorly immunogenic tumors, and more broadly, may serve as a facile platform to enable in situ personalized cancer vaccination without requiring identification of tumor-specific antigens and manufacturing of personalized vaccines. Citation Format: Miguel C. Sobral, Hua Wang, Alexander J. Najibi, Aileen Li, Catia S. Verbeke, David J. Mooney. Antigen-free cancer vaccine to treat poorly immunogenic tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B045.