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.